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Davoodi-Moghaddam Z, Jafari-Raddani F, Bashash D. Identification of Immune-Related Gene Pair Signature to Predict Prognosis of Diffuse Large B-Cell Lymphoma Based on Bioinformatics Analyses. Cancer Invest 2024; 42:858-875. [PMID: 39311546 DOI: 10.1080/07357907.2024.2405184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/11/2023] [Accepted: 09/12/2024] [Indexed: 11/20/2024]
Abstract
Since over one-third of DLBCL patients experience relapse or refractory after standard therapy, high-risk patients must be predicted. We developed a prognostic immune-related gene pairs (IRGPs) signature for DLBCL patients using bioinformatics analyses. This signature can predict the prognosis of these patients adequately, either alone or in combination with other clinical parameters. It hopes to improve the stratification and management of these patients for broad clinical applications.
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Affiliation(s)
- Zeinab Davoodi-Moghaddam
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farideh Jafari-Raddani
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Huanjie Z, Bukhari I, Fazhan L, Wen H, Wang J, Wanqing W, Yuming F, Youcai T, AlJowaie RM, Aziz IM, Xiufeng C, Yang M, Pengyuan Z. P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer. Heliyon 2024; 10:e35228. [PMID: 39166030 PMCID: PMC11334848 DOI: 10.1016/j.heliyon.2024.e35228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/22/2024] Open
Abstract
TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.
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Affiliation(s)
- Zhao Huanjie
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Ihtisham Bukhari
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Li Fazhan
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Huijuan Wen
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
| | - Jingyun Wang
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Wu Wanqing
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Fu Yuming
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Tang Youcai
- Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Reem M. AlJowaie
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Ibrahim M. Aziz
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Chu Xiufeng
- Department of Oncology, the Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
| | - Mi Yang
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
- Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China
- Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China
| | - Zheng Pengyuan
- Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, ErQi 450052, Zhengzhou, Henan, China
- Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, ErQi, 450052, Zhengzhou, Henan, China
- Academy of Medical Science, Zhengzhou University, Zhongyuan, 450001, Zhengzhou, Henan China, China
- Institute of Rehabilitation Medicine, Henan Academy of Innovations in Medical Sciences, Zhengzhou, Henan, China
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Qin L, Li B, Wang S, Tang Y, Fahira A, Kou Y, Li T, Hu Z, Huang Z. Construction of an immune-related prognostic signature and lncRNA-miRNA-mRNA ceRNA network in acute myeloid leukemia. J Leukoc Biol 2024; 116:146-165. [PMID: 38393298 DOI: 10.1093/jleuko/qiae041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 01/22/2024] [Accepted: 01/29/2024] [Indexed: 02/25/2024] Open
Abstract
The progression of acute myeloid leukemia (AML) is influenced by the immune microenvironment in the bone marrow and dysregulated intracellular competing endogenous RNA (ceRNA) networks. Our study utilized data from UCSC Xena, The Cancer Genome Atlas Program, the Gene Expression Omnibus, and the Immunology Database and Analysis Portal. Using Cox regression analysis, we identified an immune-related prognostic signature. Genomic analysis of prognostic messenger RNA (mRNA) was conducted through Gene Set Cancer Analysis (GSCA), and a prognostic ceRNA network was constructed using the Encyclopedia of RNA Interactomes. Correlations between signature mRNAs and immune cell infiltration, checkpoints, and drug sensitivity were assessed using R software, gene expression profiling interactive analysis (GEPIA), and CellMiner, respectively. Adhering to the ceRNA hypothesis, we established a potential long noncoding RNA (lncRNA)/microRNA (miRNA)/mRNA regulatory axis. Our findings pinpointed 9 immune-related prognostic mRNAs (KIR2DL1, CSRP1, APOBEC3G, CKLF, PLXNC1, PNOC, ANGPT1, IL1R2, and IL3RA). GSCA analysis revealed the impact of copy number variations and methylation on AML. The ceRNA network comprised 14 prognostic differentially expressed lncRNAs (DE-lncRNAs), 6 prognostic DE-miRNAs, and 3 prognostic immune-related DE-mRNAs. Correlation analyses linked these mRNAs' expression to 22 immune cell types and 6 immune checkpoints, with potential sensitivity to 27 antitumor drugs. Finally, we identified a potential LINC00963/hsa-miR-431-5p/CSRP1 axis. This study offers innovative insights for AML diagnosis and treatment through a novel immune-related signature and ceRNA axis. Identified novel biomarkers, including 2 mRNAs (CKLF, PNOC), 1 miRNA (hsa-miR-323a-3p), and 10 lncRNAs (SNHG25, LINC01857, AL390728.6, AC127024.5, Z83843.1, AP002884.1, AC007038.1, AC112512, AC020659.1, AC005921.3) present promising candidates as potential targets for precision medicine, contributing to the ongoing advancements in the field.
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Affiliation(s)
- Ling Qin
- Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, China
| | - Boya Li
- Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, China
| | - Shijie Wang
- Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, China
| | - Yulai Tang
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake District, Dongguan 523808, Guangdong, China
| | - Aamir Fahira
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake District, Dongguan 523808, Guangdong, China
| | - Yanqi Kou
- Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, China
| | - Tong Li
- Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang 471003, China
| | - Zhigang Hu
- School of Medical Technology and Engineering, Henan University of Science and Technology, No.263 Kaiyuan Avenue, Luolong District, Luoyang 471000, China
| | - Zunnan Huang
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake District, Dongguan 523808, Guangdong, China
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Yang B, Wang Y, Liu T, Zhang M, Luo T. The necroptosis-related signature and tumor microenvironment immune characteristics associated with clinical prognosis and drug sensitivity analysis in stomach adenocarcinoma. Aging (Albany NY) 2024; 16:6098-6117. [PMID: 38546403 PMCID: PMC11042952 DOI: 10.18632/aging.205690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 01/30/2024] [Indexed: 04/23/2024]
Abstract
PURPOSE Necroptosis plays an important role in the tumorigenesis, development, metastasis, and drug resistance of malignant tumors. This study explored the new model for assessing stomach adenocarcinoma (STAD) prognosis and immunotherapy by combining long noncoding RNAs associated with necroptosis. METHODS Patient clinical data and STAD gene expression profiles were curated from The Cancer Genome Atlas (TCGA). Immune-related genes were sourced from a specialized molecular database. Perl software and R software were used for data processing and analysis. Necroptosis-related lncRNAs in STAD were pinpointed via R's correlation algorithms. These lncRNAs, in conjunction with clinical data, informed the construction of a prognostic lncRNA-associated risk score model using univariate and multivariate Cox regression analyses. The model's prognostic capacity was evaluated by Kaplan-Meier survival curves and validated as an independent prognostic variable. Further, a nomogram incorporating this model with clinical parameters was developed, offering refined individual survival predictions. Subsequent analyses of immune infiltration and chemosensitivity within necroptosis-related lncRNA clusters utilized an arsenal of bioinformatic tools, culminating in RT-PCR validation of lncRNA expression. RESULTS Through rigorous Cox regression, 21 lncRNAs were implicated in the risk score model. Stratification by median risk scores delineated patients into high- and low-risk cohorts, with the latter demonstrating superior prognostic outcomes. The risk model was corroborated as an independent prognostic indicator for STAD. The integrative nomogram displayed high concordance between predicted and observed survival rates, as evidenced by calibration curves. Differential immune infiltration in risk-defined groups was illuminated by the single sample GSEA (ssGSEA), indicating pronounced immune presence in higher-risk patients. Tumor microenvironment (TME) analysis showed that cluster-C3 had the highest score in the analysis of the three TMEs. Through the differential analysis of immune checkpoints, it was found that almost all immune checkpoint-related genes were expressed differently in various tumor clusters. Among them, CD44 expression was the highest. By comparing all drug sensitivities, we screened out 29 drugs with differences in drug sensitivity across different clusters. Risk score gene expression identification results showed that these lncRNAs were abnormally expressed in gastric cancer cell lines. CONCLUSIONS This investigation provides a robust methodological advance in prognosticating and personalizing immunotherapy for STAD, leveraging quantitatively derived tumor cluster risk scores. It posits the use of necroptosis-related lncRNAs as pivotal molecular beacons for guiding therapeutic strategies and enhancing clinical outcomes in STAD.
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Affiliation(s)
- Biao Yang
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Yingnan Wang
- Henan University of Science and Technology, Henan 471000, China
| | - Tao Liu
- Department of Emergency, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Meijing Zhang
- Department of Oncology, Changhai Hospital, Naval Medical University, Shanghai 200433, China
| | - Tianhang Luo
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China
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Luan J, Zhang D, Liu B, Yang A, Lv K, Hu P, Yu H, Shmuel A, Zhang C, Ma G. Immune-related lncRNAs signature and radiomics signature predict the prognosis and immune microenvironment of glioblastoma multiforme. J Transl Med 2024; 22:107. [PMID: 38279111 PMCID: PMC10821572 DOI: 10.1186/s12967-023-04823-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 12/22/2023] [Indexed: 01/28/2024] Open
Abstract
BACKGROUND Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. This study aimed to construct immune-related long non-coding RNAs (lncRNAs) signature and radiomics signature to probe the prognosis and immune infiltration of GBM patients. METHODS We downloaded GBM RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database, and MRI data were obtained from The Cancer Imaging Archive (TCIA). Then, we conducted a cox regression analysis to establish the immune-related lncRNAs signature and radiomics signature. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNAs signature, radiomics signature and immune checkpoint genes. Finally, we constructed a multifactors prognostic model and compared it with the clinical prognostic model. RESULTS We identified four immune-related lncRNAs and two radiomics features, which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The risk score curves and Kaplan-Meier curves confirmed that the immune-related lncRNAs signature and radiomics signature were a novel independent prognostic factor in GBM patients. The GSEA suggested that the immune-related lncRNAs signature were involved in L1 cell adhesion molecular (L1CAM) interactions and the radiomics signature were involved signaling by Robo receptors. Besides, the two signatures was associated with the infiltration of immune cells. Furthermore, they were linked with the expression of critical immune genes and could predict immunotherapy's clinical response. Finally, the area under the curve (AUC) (0.890,0.887) and C-index (0.737,0.817) of the multifactors prognostic model were greater than those of the clinical prognostic model in both the training and validation sets, indicated significantly improved discrimination. CONCLUSIONS We identified the immune-related lncRNAs signature and tradiomics signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with GBM.
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Affiliation(s)
- Jixin Luan
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Di Zhang
- Department of Radiology, Liaocheng People's Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Liaocheng, Shandong, China
| | - Bing Liu
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Aocai Yang
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kuan Lv
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Pianpian Hu
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Hongwei Yu
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Amir Shmuel
- McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
| | - Chuanchen Zhang
- Department of Radiology, Liaocheng People's Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Liaocheng, Shandong, China.
| | - Guolin Ma
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China.
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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Zheng P, Zhang X, Ren D, Bai Q, Jiang P. Novel Immune-Related LncRNA Pairs are Associated with Immunol Infiltration and Survival Status in Glioblastoma. Neurol India 2023; 71:1226-1234. [PMID: 38174463 DOI: 10.4103/0028-3886.391381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Background Immune-related lncRNA is involved in tumor initiation and progression, while its effect in glioblastoma (GBM) is still unknown. Objective We sought to investigate the association between immune-related lncRNA (ir-lncRNA) and GBM. Methods Transcriptomic and clinical data were obtained from the TCGA dataset, and we found 2008 ir-lncRNA differentially expressed between GBM and adjacent brain tissues. Results Appling the univariate Cox and Lasso regression model, we found 30 prognosis-related ir-lncRNA pairs to construct a Cox regression risk model to associate the outcome of GBM patients. Furthermore, with this risk model, we can identify the tumor immune infiltration status, the expression of immunosuppressive biomarkers, and chemical sensitivity in GBM patients. Conclusions We constructed an immunologic risk model with lncRNA to associate the survival outcome of GBM patients, which can provide useful biomarkers.
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Affiliation(s)
- Ping Zheng
- Department of Neurosurgery, Shanghai Pudong New Area People's Hospital; Key Molecular Lab, Shanghai Pudong New Area People's Hospital, Shanghai, China
| | - Xiaoxue Zhang
- Key Molecular Lab, Shanghai Pudong New Area People's Hospital, Shanghai, China
| | - Dabin Ren
- Department of Neurosurgery, Shanghai Pudong New Area People's Hospital, Shanghai, China
| | - Qingke Bai
- Department of Neurology, Shanghai Pudong New Area People's Hospital, Shanghai, China
| | - Ping Jiang
- Department of Nursing, Shanghai Pudong New Area People's Hospital, Shanghai, China
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Han L, Wang Z, Li C, Fan M, Wang Y, Sun G, Dai G. Functional identification and prediction of lncRNAs in esophageal cancer. Comput Biol Med 2023; 165:107205. [PMID: 37611425 DOI: 10.1016/j.compbiomed.2023.107205] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/29/2023] [Accepted: 06/25/2023] [Indexed: 08/25/2023]
Abstract
Esophageal cancer is a highly lethal malignancy with poor prognosis, and the identification of molecular biomarkers is crucial for improving diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of esophageal cancer. However, due to the time cost of biological experiments, only a small number of lncRNAs related to esophageal cancer have been discovered. Currently, computational methods have emerged as powerful tools for identifying and characterizing lncRNAs, as well as predicting their potential functions. Therefore, this article proposes a transformer-based method for identifying esophageal cancer-related lncRNAs. Experimental results show that the AUC and AUPR of this method are superior to other comparison methods, with an AUC of 0.87 and an AUPR of 0.83, and the identified lncRNA targets are closely associated with esophageal cancer. We focus on the role of esophageal cancer-related lncRNAs in the immune microenvironment, and fully explore the functions of the target genes regulated by lncRNAs. Enrichment analysis shows that the predicted target genes are related to multiple pathways involved in the occurrence, development, and prognosis of esophageal cancer. This not only demonstrates the effectiveness of the method but also indicates the accuracy of the prediction results.
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Affiliation(s)
- Lu Han
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Zhikuan Wang
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Congyong Li
- Medical School of Chinese PLA, Beijing, China; Sixth Health Care Department, The Second Medical Center of PLA General Hospital, Beijing, China
| | - Mengjiao Fan
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Yanrong Wang
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
| | - Guanghai Dai
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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Zhang Y, Wang Y, He X, Yao R, Fan L, Zhao L, Lu B, Pang Z. Genome instability-related LINC02577, LINC01133 and AC107464.2 are lncRNA prognostic markers correlated with immune microenvironment in pancreatic adenocarcinoma. BMC Cancer 2023; 23:430. [PMID: 37173624 PMCID: PMC10176692 DOI: 10.1186/s12885-023-10831-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 04/09/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma (PAAD) is a leading cause of malignancy-related deaths worldwide, and the efficacy of immunotherapy on PAAD is limited. Studies report that long non-coding RNAs (lncRNAs) play an important role in modulating genomic instability and immunotherapy. However, the identification of genome instability-related lncRNAs and their clinical significance has not been investigated in PAAD. METHODS The current study developed a computational framework for mutation hypothesis based on lncRNA expression profile and somatic mutation spectrum in pancreatic adenocarcinoma genome. We explored the potential of GInLncRNAs(genome instability-related lncRNAs) through co-expression analysis and function enrichment analysis. We further analyzed GInLncRNAs by Cox regression and used the results to construct a prognostic lncRNA signature. Finally, we analyzed the relationship between GILncSig (genomic instability derived 3-lncRNA signature) and immunotherapy. RESULTS A GILncSig was developed using bioinformatics analyses. It could divide patients into high-risk and low-risk groups, and there was a significant difference in OS between the two groups. In addition, GILncSig was associated with genome mutation rate in pancreatic adenocarcinoma, indicating its potential value as a marker for genomic instability. The GILncSig accurately grouped wild type patients of KRAS into two risk groups. The prognosis of the low-risk group was significantly improved. GILncSig was significantly correlated with the level of immune cell infiltration and immune checkpoint. CONCLUSIONS In summary, the current study provides a basis for further studies on the role of lncRNA in genomic instability and immunotherapy. The study provides a novel method for identification of cancer biomarkers related to genomic instability and immunotherapy.
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Affiliation(s)
- Yinjiang Zhang
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China
| | - Yao Wang
- Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xu He
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China
| | - Rongfei Yao
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China
| | - Lu Fan
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China
| | - Linyi Zhao
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China
| | - Binan Lu
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China.
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China.
| | - Zongran Pang
- School of Pharmacy, Minzu University of China, No. 27, Zhongguancunnan Street, Haidian District, Beijing, 100081, People's Republic of China.
- Key Laboratory of Ethnomedicine, Ministry of Education, Minzu University of China), Beijing, People's Republic of China.
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Ma S, Zhao H, Wang F, Peng L, Zhang H, Wang Z, Jiang F, Zhang D, Yin M, Li S, Huang J, Liu Z, Tao S. Integrative analysis to screen novel pyroptosis-related LncRNAs for predicting clinical outcome of glioma and validation in tumor tissue. Aging (Albany NY) 2023; 15:1628-1651. [PMID: 36917093 PMCID: PMC10042692 DOI: 10.18632/aging.204580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/20/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND Pyroptosis, also known as inflammatory necrosis, is a programmed cell death that manifests itself as a continuous swelling of cells until the cell membrane breaks, leading to the liberation of cellular contents, which triggers an intense inflammatory response. Pyroptosis might be a panacea for a variety of cancers, which include immunotherapy and chemotherapy-insensitive tumors such as glioma. Several findings have observed that long non-coding RNAs (lncRNAs) modulate the bio-behavior of tumor cells by binding to RNA, DNA and protein. Nevertheless, there are few studies reporting the effect of lncRNAs in pyroptosis processes in glioma. METHODS The principal goal of this study was to identify pyroptosis-related lncRNAs (PRLs) utilizing bioinformatic algorithm and to apply PCR techniques for validation in human glioma tissues. The second goal was to establish a prognostic model for predicting the overall survival patients with glioma. Predict algorithm was used to construct prognosis model with good diagnostic precision for potential clinical translation. RESULTS Noticeably, molecular subtypes categorized by the PRLs were not distinct from any previously published subtypes of glioma. The immune and mutation landscapes were obviously different from previous subtypes of glioma. Analysis of the sensitivity (IC50) of patients to 30 chemotherapeutic agents identified 22 agents as potential therapeutic agents for patients with low riskscores. CONCLUSIONS We established an exact prognostic model according to the expression profile of PRLs, which may facilitate the assessment of patient prognosis and treatment patterns and could be further applied to clinical.
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Affiliation(s)
- Shuai Ma
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310006, China
- Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
| | - Hongtao Zhao
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310006, China
| | - Fang Wang
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310006, China
| | - Lulu Peng
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Heng Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Zaibin Wang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Fan Jiang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Dongtao Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Menglei Yin
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Shupeng Li
- Department of Neurosurgery, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116000, China
| | - Jiaming Huang
- Department of Neurosurgery, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian 116000, China
| | - Zhan Liu
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
| | - Shengzhong Tao
- Department of Neurosurgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450053, China
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Zhang X, Yang L, Zhang D, Wang X, Bu X, Zhang X, Cui L. Prognostic assessment capability of a five-gene signature in pancreatic cancer: a machine learning based-study. BMC Gastroenterol 2023; 23:68. [PMID: 36906533 PMCID: PMC10007739 DOI: 10.1186/s12876-023-02700-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 02/27/2023] [Indexed: 03/13/2023] Open
Abstract
BACKGROUND A prognostic assessment method with good sensitivity and specificity plays an important role in the treatment of pancreatic cancer patients. Finding a way to evaluate the prognosis of pancreatic cancer is of great significance for the treatment of pancreatic cancer. METHODS In this study, GTEx dataset and TCGA dataset were merged together for differential gene expression analysis. Univariate Cox regression and Lasso regression were used to screen variables in the TCGA dataset. Screening the optimal prognostic assessment model is then performed by gaussian finite mixture model. Receiver operating characteristic (ROC) curves were used as an indicator to assess the predictive ability of the prognostic model, the validation process was performed on the GEO datasets. RESULTS Gaussian finite mixture model was then used to build 5-gene signature (ANKRD22, ARNTL2, DSG3, KRT7, PRSS3). Receiver operating characteristic (ROC) curves suggested the 5-gene signature performed well on both the training and validation datasets. CONCLUSIONS This 5-gene signature performed well on both our chosen training dataset and validation dataset and provided a new way to predict the prognosis of pancreatic cancer patients.
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Affiliation(s)
- Xuanfeng Zhang
- Center of Hepatobiliary Pancreatic Disease, XuZhou Central Hospital, Jiangsu, People's Republic of China.,Center of Hepatobiliary Pancreatic Disease, The Affiliated Xuzhou Hospital of Medical School of Southeast University, No.199 Jiefang South Road, Xuzhou, Jiangsu, People's Republic of China
| | - Lulu Yang
- Department of Radiology, XuZhou Central Hospital, Jiangsu, People's Republic of China.,Department of Radiology, The Affiliated Xuzhou Hospital of Medical School of Southeast University, Jiangsu, People's Republic of China
| | - Dong Zhang
- Center of Hepatobiliary Pancreatic Disease, XuZhou Central Hospital, Jiangsu, People's Republic of China.,Bengbu Medical College, Anhui, People's Republic of China
| | - Xiaochuan Wang
- Center of Hepatobiliary Pancreatic Disease, XuZhou Central Hospital, Jiangsu, People's Republic of China.,Center of Hepatobiliary Pancreatic Disease, The Affiliated Xuzhou Hospital of Medical School of Southeast University, No.199 Jiefang South Road, Xuzhou, Jiangsu, People's Republic of China
| | - Xuefeng Bu
- Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China
| | - Xinhui Zhang
- Center of Hepatobiliary Pancreatic Disease, XuZhou Central Hospital, Jiangsu, People's Republic of China. .,Center of Hepatobiliary Pancreatic Disease, The Affiliated Xuzhou Hospital of Medical School of Southeast University, No.199 Jiefang South Road, Xuzhou, Jiangsu, People's Republic of China.
| | - Long Cui
- Center of Hepatobiliary Pancreatic Disease, XuZhou Central Hospital, Jiangsu, People's Republic of China. .,Center of Hepatobiliary Pancreatic Disease, The Affiliated Xuzhou Hospital of Medical School of Southeast University, No.199 Jiefang South Road, Xuzhou, Jiangsu, People's Republic of China.
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11
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Su X, Gao H, Qi Z, Xu T, Wang G, Luo H, Cheng P. Prediction of immune subtypes and overall survival in lung squamous cell carcinoma. Curr Med Res Opin 2023; 39:289-298. [PMID: 36245361 DOI: 10.1080/03007995.2022.2129231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVE Lung squamous cell carcinoma (LUSC), one of the most common subtypes of lung cancer, is a leading cause of cancer-caused deaths in the world. It has been well demonstrated that a deep understanding of the tumor environment in cancer would be helpful to predict the prognosis of patients. This study aimed to evaluate the tumor environment in LUSC, and to construct an efficient prognosis model involved in specific subtypes. METHODS Four expression files were downloaded from the Gene Expression Omnibus (GEO) database. Three datasets (GSE19188, GSE2088, GSE6044) were considered as the testing group and the other dataset (GSE11969) was used as the validation group. By performing LUSC immune subtype consensus clustering (CC), LUSC patients were separated into two immune subtypes comprising subtype 1 (S1) and subtype 2 (S2). Weighted gene co-expression network (WGCNA) and least absolute shrinkage and selection operator (LASSO) were performed to identify and narrow down the key genes among subtype 1 related genes that were closely related to the overall survival (OS) of LUSC patients. Using immune subtype related genes, a prognostic model was also constructed to predict the OS of LUSC patients. RESULTS It showed that LUSC patients in the S1 immune subtype exhibited a better OS than in the S2 immune subtype. WGCNA and LASSO analyses screened out important immune subtype related genes in specific modules that were closely associated with LUSC prognosis, followed by construction of the prognostic model. Both the testing datasets and validation dataset confirmed that the prognostic model could be efficiently used to predict the OS of LUSC patients in subtype 1. CONCLUSION We explored the tumor environment in LUSC and established a risk prognostic model that might have the potential to be applied in clinical practice.
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Affiliation(s)
- Xiaomei Su
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Hui Gao
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Zhongchun Qi
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Tao Xu
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Guangjie Wang
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Hong Luo
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
| | - Peng Cheng
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu City, Sichuan Province, P.R. China
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12
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Li J, Li W, Wang H, Ni B, Liu Y. Development and validation of a novel ferroptosis‑related lncRNA prognostic signature for pancreatic adenocarcinoma. Mol Med Rep 2023; 27:56. [PMID: 36660936 PMCID: PMC9879080 DOI: 10.3892/mmr.2023.12943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 11/29/2022] [Indexed: 01/19/2023] Open
Abstract
Long non‑coding RNAs (lncRNAs) serve a pivotal role in the regulation of cancer cell ferroptosis. However, the prognostic value of ferroptosis‑related lncRNAs in pancreatic adenocarcinoma (PAAD) largely remains unclear. We aimed at constructing a lncRNA‑based signature to improve the prognosis prediction of PAAD. In the present study, the transcriptome profiling data and clinical information of patients with PAAD were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Gene Consortium (ICGC) databases. Univariate Cox regression analysis of the TCGA cohort demonstrated that 26 ferroptosis‑related lncRNAs had significant prognostic value for PAAD (all P<0.01). Least absolute shrinkage and selection operator regression and multivariate Cox proportional hazards regression analyses were performed to construct a prognostic ferroptosis‑related lncRNA signature (FRLS) comprising nine ferroptosis‑related lncRNAs. The efficacy of this FRLS was verified in the training (TCGA) and validation (ICGC) cohorts. Based on the risk model, high risk scores were significantly correlated with poor overall survival (OS) (hazard ratio, 1.314; 95% confidence interval, 1.218‑1.418; P<0.001). The receiver operating characteristic curves and principal component analysis further demonstrated the robust prognostic ability of the FRLS. Furthermore, a nomogram with favorable predictive efficacy for the prediction of OS was constructed based on the FRLS and clinical features. Gene set enrichment analysis demonstrated that the genes in the FRLS participated in a number of cancer‑associated immunoregulatory pathways. Importantly, it was demonstrated that immune infiltration and response to cancer immunotherapy differed significantly between the high and low‑risk groups according to the FRLS. In conclusion, the risk signature based on the FRLS has potential for the clinical prediction of prognosis and immunotherapy response in patients with PAAD.
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Affiliation(s)
- Jian Li
- Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China,Department of General Surgery, Air Force Hospital of Western Theater Command, Chengdu, Sichuan 610065, P.R. China,Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Wenhua Li
- Department of Cadre Ward, Air Force Hospital of Western Theater Command, Chengdu, Sichuan 610065, P.R. China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Bing Ni
- Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China,Correspondence to: Professor Bing Ni, Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, 30 Gaotanyan Main Street, Shapingba, Chongqing 400038, P.R. China, E-mail:
| | - Yongkang Liu
- Department of General Surgery, Air Force Hospital of Western Theater Command, Chengdu, Sichuan 610065, P.R. China,Dr Yongkang Liu, Department of General Surgery, Air Force Hospital of Western Theater Command, 18 Shunjiang Street, Jinjiang, Chengdu, Sichuan 610065, P.R. China, E-mail:
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LncRNA MBNL1-AS1 Suppresses Cell Proliferation and Metastasis of Pancreatic Adenocarcinoma through Targeting Carcinogenic miR-301b-3p. Genet Res (Camb) 2023; 2023:6785005. [PMID: 36908851 PMCID: PMC9995204 DOI: 10.1155/2023/6785005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/20/2023] [Accepted: 02/13/2023] [Indexed: 03/05/2023] Open
Abstract
Pancreatic adenocarcinoma (PAAD) has been a huge challenge to public health due to its increasing incidence, frequent early metastasis, and poor outcome. The molecular basis of tumorigenesis and metastasis in PAAD is largely unclear. Here, we identified a novel tumor-suppressor long noncoding RNA (lncRNA) MBNL1-AS1, in PAAD and revealed its downstream mechanism. Quantitative real-time PCR (qRT-PCR) data showed that MBNL1-AS1 expression was significantly downregulated in PAAD tissues and cells, which was closely associated with metastasis and poor prognosis. Cell counting kit-8 (CCK-8) assay, transwell assay, and western blot verified that overexpression of MBNL1-AS1 suppressed cell proliferation, migration, and epithelial mesenchymal transformation (EMT) behavior in PAAD cells. By using a dual luciferase reporter gene system, we confirmed that miR-301b-3p was a direct target of MBNL1-AS1. Further mechanismic study revealed that upregulation of miR-301b-3p abolished the inhibitory effect of MBNL1-AS1 overexpression on cell proliferation, tumorigenesis, migration and EMT. Our results demonstrate that MBNL1-AS1 plays a tumor-suppressive role in PAAD mainly by downregulating miR-301b-3p, providing a novel therapeutic target for PAAD.
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Kang Y, Xu X, Liu J. System Analysis Based on Pancreatic Cancer Progression Identifies BRINP2 as a Novel Prognostic Biomarker. Crit Rev Eukaryot Gene Expr 2023; 33:1-16. [PMID: 37602449 DOI: 10.1615/critreveukaryotgeneexpr.2023048337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system, which develops rapidly and has no obvious early symptoms. This study aims to discover the biomarkers associated with PAAD development. We obtained RNA expression of PAAD patient samples and corresponding clinical data from The cancer genome atlas (TCGA), and screened out BMP/RA-inducible neural-specific protein 2 (BRINP2) gene which is highly associated with PAAD severity. Then, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and single-sample gene set enrichment analysis (ssGSEA) analysis were performed to explore the biological functions of BRINP2. Subsequently, long non-coding RNA (lncRNAs) associated with BRINP2 were screened out via correlation analysis, and Cox regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were used to construct the risk prediction model. We further validated the expression level of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in vitro. We proposed that BRINP2 might be correlated to the tumor immune microenvironment and could also be used as a biomarker for PAAD progression. GO enrichment analysis and KEGG pathway analysis showed that the prognostic model was highly correlated to immune microenvironment-related pathways. Additionally, we established a BRINP2-associated lncRNAs prognostic model consisting of three lncRNAs. We validated the expression trends of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in PAAD cells with various severity of metastatic potential using the quantitative real-time PCR (qRT-PCR). Meanwhile, pRRophetic R package was employed to predict potential therapeutic drugs for BRINP2-associated lncRNAs prognostic model of PAAD. The results suggest that BRINP2 can be used as a novel prognostic biomarker for PAAD.
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Affiliation(s)
- Yixing Kang
- Department of Clinical Medicine, Weifang Medical University, Weifang 261031, China
| | - Xiangwen Xu
- Department of Plastic and Reconstructive Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Jikui Liu
- Department of Hepatobiliary and Pancreatic Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
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Grandt CL, Brackmann LK, Poplawski A, Schwarz H, Marini F, Hankeln T, Galetzka D, Zahnreich S, Mirsch J, Spix C, Blettner M, Schmidberger H, Marron M. Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls. Front Oncol 2023; 13:1158176. [PMID: 37182169 PMCID: PMC10174438 DOI: 10.3389/fonc.2023.1158176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/27/2023] [Indexed: 05/16/2023] Open
Abstract
Introduction Long non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular. Methods Primary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function. Results After irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation). Discussion For the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response.
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Affiliation(s)
- Caine Lucas Grandt
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
- Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
- *Correspondence: Caine Lucas Grandt,
| | - Lara Kim Brackmann
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
| | - Alicia Poplawski
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Heike Schwarz
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
| | - Federico Marini
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Thomas Hankeln
- Institute of Organismic and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Danuta Galetzka
- Department of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Sebastian Zahnreich
- Department of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Johanna Mirsch
- Radiation Biology and DNA Repair, Technical University of Darmstadt, Darmstadt, Germany
| | - Claudia Spix
- Division of Childhood Cancer Epidemiology, German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Maria Blettner
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Heinz Schmidberger
- Department of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Manuela Marron
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
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Zhou L, Wang C. Diagnosis and prognosis prediction model for digestive system tumors based on immunologic gene sets. Front Oncol 2023; 13:1107532. [PMID: 36937448 PMCID: PMC10020235 DOI: 10.3389/fonc.2023.1107532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/17/2023] [Indexed: 03/06/2023] Open
Abstract
According to 2020 global cancer statistics, digestive system tumors (DST) are ranked first in both incidence and mortality. This study systematically investigated the immunologic gene set (IGS) to discover effective diagnostic and prognostic biomarkers. Gene set variation (GSVA) analysis was used to calculate enrichment scores for 4,872 IGSs in patients with digestive system tumors. Using the machine learning algorithm XGBoost to build a classifier that distinguishes between normal samples and cancer samples, it shows high specificity and sensitivity on both the validation set and the overall dataset (area under the receptor operating characteristic curve [AUC]: validation set = 0.993, overall dataset = 0.999). IGS-based digestive system tumor subtypes (IGTS) were constructed using a consistent clustering approach. A risk prediction model was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) method. DST is divided into three subtypes: subtype 1 has the best prognosis, subtype 3 is the second, and subtype 2 is the worst. The prognosis model constructed using nine gene sets can effectively predict prognosis. Prognostic models were significantly associated with tumor mutational burden (TMB), tumor immune microenvironment (TIME), immune checkpoints, and somatic mutations. A composite nomogram was constructed based on the risk score and the patient's clinical information, with a well-fitted calibration curve (AUC = 0.762). We further confirmed the reliability and validity of the diagnostic and prognostic models using other cohorts from the Gene Expression Omnibus database. We identified diagnostic and prognostic models based on IGS that provide a strong basis for early diagnosis and effective treatment of digestive system tumors.
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Affiliation(s)
- Lin Zhou
- School of Information Science and Technology, University of Science and Technology of China, Hefei, Anhui, China
| | - Chunyu Wang
- School of Biological and Environmental Engineering, Chaohu University, Chaohu, Anhui, China
- *Correspondence: Chunyu Wang,
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Li X, Qin H, Anwar A, Zhang X, Yu F, Tan Z, Tang Z. Molecular mechanism analysis of m6A modification-related lncRNA-miRNA-mRNA network in regulating autophagy in acute pancreatitis. Islets 2022; 14:184-199. [PMID: 36218109 PMCID: PMC9559333 DOI: 10.1080/19382014.2022.2132099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
This study aims to explore the molecular mechanism of N6-methyladenosine (m6A) modification-related long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network in regulating autophagy and affecting the occurrence and development of acute pancreatitis (AP). RNA-seq datasets related to AP were obtained from Gene Expression Omnibus (GEO) database and merged after batch effect removal. lncRNAs significantly related to m6A in AP, namely candidate lncRNA, were screened by correlation analysis and differential expression analysis. In addition, candidate autophagy genes were screened through the multiple databases. Furthermore, the key pathways for autophagy to play a role in AP were determined by functional enrichment analysis. Finally, we predicted the miRNAs binding to genes and lncRNAs through TargetScan, miRDB and DIANA TOOLS databases and constructed two types of lncRNA-miRNA-mRNA regulatory networks mediated by upregulated and downregulated lncRNAs in AP. Nine lncRNAs related to m6A were differentially expressed in AP, and 21 candidate autophagy genes were obtained. Phosphoinositide 3-kinase (PI3K)-Akt signaling pathway and Forkhead box O (FoxO) signaling pathway might be the key pathways for autophagy to play a role in AP. Finally, we constructed a lncRNA-miRNA-mRNA regulatory network. An upregulated lncRNA competitively binds to 13 miRNAs to regulate 6 autophagy genes, and a lncRNA-miRNA-mRNA regulatory network in which 2 downregulated lncRNAs competitively bind to 7 miRNAs to regulate 2 autophagy genes. m6A modification-related lncRNA Pvt1, lncRNA Meg3 and lncRNA AW112010 may mediate the lncRNA-miRNA-mRNA network, thereby regulating autophagy to affect the development of AP.
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Affiliation(s)
- Xiang Li
- Critical Care Unit, the First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- Emergency Department (one), Hunan Provincial People’s Hospital, Changsha, Hunan, P.R. China
| | - Hong Qin
- Xiangya School of Public Health, Central South University, Changsha, P.R. China
| | - Ali Anwar
- Xiangya School of Public Health, Central South University, Changsha, P.R. China
- Food and Nutrition Society Gilgit Baltistan, Pakistan
| | - Xingwen Zhang
- Emergency Department (three), Hunan Provincial People’s Hospital, Changsha, Hunan, P.R. China
| | - Fang Yu
- Emergency Department (one), Hunan Provincial People’s Hospital, Changsha, Hunan, P.R. China
| | - Zheng Tan
- Emergency Department (one), Hunan Provincial People’s Hospital, Changsha, Hunan, P.R. China
| | - Zhanhong Tang
- Critical Care Unit, the First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China
- CONTACT Zhanhong Tang Critical Care Unit, the First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning530021, Guangxi, P.R. China
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Li H, Liu ZY, Chen YC, Zhang XY, Wu N, Wang J. Identification and validation of an immune-related lncRNAs signature to predict the overall survival of ovarian cancer. Front Oncol 2022; 12:999654. [PMID: 36313727 PMCID: PMC9596922 DOI: 10.3389/fonc.2022.999654] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 09/27/2022] [Indexed: 12/23/2022] Open
Abstract
Ovarian cancer (OC) is the most lethal gynecological cancer in women. Studies had reported that immune-related lncRNAs signatures were valuable in predicting the survival and prognosis of patients with various cancers. In our study, the prognostic value of immune-related lncRNAs was investigated in OC patients from TCGA-RNA-seq cohort (n=378) and HG-U133_Plus_2 cohort (n=590), respectively. Pearson correlation analysis was implemented to screen the immune-related lncRNA and then univariate Cox regression analysis was performed to explore their prognostic value in OC patients. Five prognostic immune-related lncRNAs were identified as prognostic lncRNAs. Besides, they were inputted into a LASSO Cox regression to establish and validate an immune-related lncRNA prognostic signature in TCGA-RNA-Seq cohort and HG-U133_Plus_2 cohort, respectively. Based on the best cut-off value of risk score, patients were divided into high- and low-risk groups. Survival analysis suggested that patients in the high-risk group had a worse overall survival (OS) than those in the low-risk group in both cohorts. The association between clinicopathological feathers and risk score was then evaluated by using stratification analysis. Moreover, we constructed a nomogram based on risk score, age and stage, which had a strong ability to forecast the OS of the OC patients. The influence of risk score on immune infiltration and immunotherapy response were assessed and the results suggested that patients with high-risk score might recruit multiple immune cells and stromal cells, leading to facilitating immune surveillance evasive. Ultimately, we demonstrated that the risk model was associated with chemotherapy response of multiple antitumor drugs, especially for paclitaxel, metformin and veliparib, which are commonly used in treating OC patients. In conclusion, we constructed a novel immune-related lncRNA signature, which had a potential prognostic value for OC patients and might facilitate personalized counselling for immunotherapy and chemotherapy.
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Affiliation(s)
- He Li
- The Animal Laboratory Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Zhao-Yi Liu
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yong-Chang Chen
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Xiao-Ye Zhang
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Nayiyuan Wu
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- *Correspondence: Jing Wang, ; Nayiyuan Wu,
| | - Jing Wang
- The Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Department of Gynecologic Cancer, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- *Correspondence: Jing Wang, ; Nayiyuan Wu,
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Ye Y, Zhao Q, Wu Y, Wang G, Huang Y, Sun W, Zhang M. Construction of a cancer-associated fibroblasts-related long non-coding RNA signature to predict prognosis and immune landscape in pancreatic adenocarcinoma. Front Genet 2022; 13:989719. [PMID: 36212154 PMCID: PMC9538573 DOI: 10.3389/fgene.2022.989719] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/12/2022] [Indexed: 11/23/2022] Open
Abstract
Background: Cancer-associated fibroblasts (CAFs) are an essential cell population in the pancreatic cancer tumor microenvironment and are extensively involved in drug resistance and immune evasion mechanisms. Long non-coding RNAs (lncRNAs) are involved in pancreatic cancer evolution and regulate the biological behavior mediated by CAFs. However, there is a lack of understanding of the prognostic signatures of CAFs-associated lncRNAs in pancreatic cancer patients. Methods: Transcriptomic and clinical data for pancreatic adenocarcinoma (PAAD) and the corresponding mutation data were obtained from The Cancer Genome Atlas database. lncRNAs associated with CAFs were obtained using co-expression analysis. lncRNAs were screened by Cox regression analysis using least absolute shrinkage and selection operator (LASSO) algorithm for constructing predictive signature. According to the prognostic model, PAAD patients were divided into high-risk and low-risk groups. Kaplan-Meier analysis was used for survival validation of the model in the training and validation groups. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. The gene set variation analysis (GSVA) and gene ontology (GO) analyses were used to explore differences in the biological behavior of the risk groups. Furthermore, single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), ESTIMATE algorithm, and a series of immune correlation analyses were performed to investigate the relationship between predictive signature and the tumor immune microenvironment and screen for potential responders to immune checkpoint inhibitors. Finally, drug sensitivity analyses were used to explore potentially effective drugs in high- and low-risk groups. Results: The signature was constructed with seven CAFs-related lncRNAs (AP005233.2, AC090114.2, DCST1-AS1, AC092171.5, AC002401.4, AC025048.4, and CASC8) that independently predicted the prognosis of PAAD patients. Additionally, the high-risk group of the model had higher TMB levels than the low-risk group. Immune correlation analysis showed that most immune cells, including CD8+ T cells, were negatively correlated with the model risk scores. ssGSEA and ESTIMATE analyses further indicated that the low-risk group had a higher status of immune cell infiltration. Meanwhile, the mRNA of most immune checkpoint genes, including PD1 and CTLA4, were highly expressed in the low-risk group, suggesting that this population may be “hot immune tumors” and have a higher sensitivity to immune checkpoint inhibitors (ICIs). Finally, the predicted half-maximal inhibitory concentrations of some chemical and targeted drugs differ between high- and low-risk groups, providing a basis for treatment selection. Conclusion: Our findings provide promising insights into lncRNAs associated with CAFs in PAAD and provide a personalized tool for predicting patient prognosis and immune microenvironmental landscape.
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Affiliation(s)
- Yingquan Ye
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
| | - Qinying Zhao
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
| | - Yue Wu
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
| | - Gaoxiang Wang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
| | - Yi Huang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
| | - Weijie Sun
- Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Weijie Sun, ; Mei Zhang,
| | - Mei Zhang
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, Hefei, China
- *Correspondence: Weijie Sun, ; Mei Zhang,
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Li X, Yang L, Wang W, Rao X, Lai Y. Constructing a prognostic immune-related lncRNA model for colon cancer. Medicine (Baltimore) 2022; 101:e30447. [PMID: 36197160 PMCID: PMC9509170 DOI: 10.1097/md.0000000000030447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 07/29/2022] [Indexed: 11/25/2022] Open
Abstract
Colon cancer is a common digestive tract tumor. Although many gene prognostic indicators have been used to predict the prognosis of colon cancer patients, the accuracy of these prognostic indicators is still uncertain. Thus, it is necessary to construct a model for the prognostic analysis of colon cancer. We downloaded the original transcriptome data of colon cancer and performed a differential coexpression analysis of immune-related genes to obtain different immune-related long noncoding RNAs, which were paired as differentially expressed immune-related lncRNA pairs (DEirlncRNAPs). Then, the 1-year overall survival rate receiver operating characteristic curve was calculated, and the Akaike information criterion value was evaluated to determine the maximum inflection point, which was used as the cutoff point to identify groups of colon cancer patients at high and low risk for death. Subsequently, the optimal prediction model was established. Finally, we used the patients' survival times, clinicopathological features, tumor infiltrating immune cells, chemotherapy responses, and immunosuppressive biomarkers to verify the DEirlncRNAP model. Seventy-one DEirlncRNAPs were obtained to build the risk assessment model. The patients were divided into a high-risk group and a low-risk group according to the cutoff point. Then, the DEirlncRNAP model was verified using patient survival times, clinicopathological features, tumor-infiltrating immune cells, chemotherapy responses, and immunosuppressive biomarkers. A new DEirlncRNAP model for predicting the prognosis of colon cancer patients was established, which could reveal new insights into the relationships of colon cancer with tumor-infiltrating immune cells and antitumor immunotherapy.
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Affiliation(s)
- Xinyun Li
- School of Traditional Chinese Medicine, Sichuan College of Traditional Chinese Medicine, China
| | - Lin Yang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen Wang
- School of Traditional Chinese Medicine, Sichuan College of Traditional Chinese Medicine, China
| | - Xiangshu Rao
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Lai
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Xu C, Qin C, Jian J, Peng Y, Wang X, Chen X, Wu D, Song Y. Identification of an immune-related gene signature as a prognostic target and the immune microenvironment for adrenocortical carcinoma. Immun Inflamm Dis 2022; 10:e680. [PMID: 36039643 PMCID: PMC9382862 DOI: 10.1002/iid3.680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 07/01/2022] [Accepted: 07/04/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Even with complete tumor resection and adjuvant therapies, the prognosis of patients with ACC remains unsatisfactory. In the microtumor environment, the impact of a disordered immune system and abnormal immune responses is enormous. To improve treatment, novel prognostic predictors and treatment targets for ACC need to be identified. Hence, credible prognostic biomarkers of immune-associated genes (IRGs) should be explored and developed. MATERIAL AND METHODS We downloaded RNA-sequencing data and clinical data from The Cancer Genome Atlas (TCGA) data set, Genotype-Tissue Expression data set, and Gene Expression Omnibus data set. Gene set enrichment analysis (GSEA) was applied to reveal the potential functions of differentially expressed genes. RESULTS GSEA indicated an association between ACC and immune-related functions. We obtained 332 IRGs and constructed a prognostic signature on the strength of 3 IRGs (INHBA, HELLS, and HDAC4) in the training cohort. The high-risk group had significantly poorer overall survival than the low-risk group (p < .001). Multivariate Cox regression was performed with the signature as an independent prognostic indicator for ACC. The testing cohort and the entire TCGA ACC cohort were utilized to validate these findings. Moreover, external validation was conducted in the GSE10927 and GSE19750 cohorts. The tumor-infiltrating immune cells analysis indicated that the quantity of T cells, natural killer cells, macrophage cells, myeloid dendritic cells, and mast cells in the immune microenvironment differed between the low-risk and high-risk groups. CONCLUSION Our three-IRG prognostic signature and the three IRGs can be used as prognostic indicators and potential immunotherapeutic targets for ACC. Inhibitors of the three novel IRGs might activate immune cells and play a synergistic role in combination therapy with immunotherapy for ACC in the future.
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Affiliation(s)
- Chengdang Xu
- Department of Urology, Tongji Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Caipeng Qin
- Department of UrologyPeking University People's HospitalBeijingChina
| | - Jingang Jian
- Department of Urology, The First Affiliated Hospital of Soochow University, Dushu Lake Hospital Affiliated to Soochow UniversitySuzhou Medical College of Soochow UniversitySuzhouChina
| | - Yun Peng
- Department of UrologyPeking University People's HospitalBeijingChina
| | - Xinan Wang
- Department of Urology, Tongji Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Xi Chen
- Department of Urology, Tongji Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Denglong Wu
- Department of Urology, Tongji Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Yuxuan Song
- Department of UrologyPeking University People's HospitalBeijingChina
- Department of UrologyTianjin Medical University General HospitalTianjinChina
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Li M, Mao S, Li L, Wei M. Hypoxia-related LncRNAs signature predicts prognosis and is associated with immune infiltration and progress of head and neck squamous cell carcinoma. Biochem Biophys Rep 2022; 31:101304. [PMID: 35818500 PMCID: PMC9270212 DOI: 10.1016/j.bbrep.2022.101304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/17/2022] [Accepted: 06/26/2022] [Indexed: 12/21/2022] Open
Abstract
Background Disclosing prognostic information is necessary to enable good treatment selection and improve patient outcomes. Previous studies suggest that hypoxia is associated with an adverse prognosis in patients with HNSCC and that long non-coding RNAs (lncRNAs) show functions in hypoxia-associated cancer biology. Nevertheless, the understanding of lncRNAs in hypoxia related HNSCC progression remains confusing. Methods Data were downloaded from TCGA and GEO database. Bioinformatic tools including R packages GEOquery, limma, pheatmap, ggplot2, clusterProfiler, survivalROC and survcomp and LASSO cox analysis were utilized. Si-RNA transfection, CCK8 and real-time quantified PCR were used in functional study. Results GEO data (GSE182734) revealed that lncRNA regulation may be important in hypoxia related response of HNSCC cell lines. Further analysis in TCGA data identified 314 HRLs via coexpression analysis between differentially expressed lncRNAs and hypoxia-related mRNAs. 23 HRLs were selected to build the prognosis predicting model using lasso Cox regression analyses. Our model showed excellent performance in predicting survival outcomes among patients with HNSCC in both the training and validation sets. We also found that the risk scores were related to tumor stage and to tumor immune infiltration. Moreover, LINC01116 were selected as a functional study target. The knockdown of LINC01116 significantly inhibited the proliferation of HNSCC cells and effected the hypoxia induced immune and the NF-κB/AKT signaling. Conclusions Data analysis of large cohorts and functional experimental validation in our study suggest that hypoxia related lncRNAs play an important role in the progression of HNSCC, and its expression model can be used for prognostic prediction.
NcRNAs regulations showed significance in hypoxia related response in HNSCC. 314 lncRNAs coexpressed with hypoxia marker genes were identified as HRLs. An effective HRLs prognosis prediction model had been constructed and validated. Immune cells and pathways paly roles in hypoxia related progress of HNSCC. LINC01116 regulates HNSCC through hypoxia related immune and NF-κB/AKT signaling.
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Affiliation(s)
- Minhan Li
- School of Stomatology, Shandong University, Jinan, Shandong, China
| | - Shaowei Mao
- School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China
| | - Lixing Li
- Department of General Surgery, Shanghai Xuhui District Central Hospital, Shanghai, China
| | - Muyun Wei
- School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China
- Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
- Corresponding author. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China
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Wang Y, Lu G, Xue X, Xie M, Wang Z, Ma Z, Feng Y, Shao C, Duan H, Pan M, Ding P, Li X, Han J, Yan X. Characterization and validation of a ferroptosis-related LncRNA signature as a novel prognostic model for lung adenocarcinoma in tumor microenvironment. Front Immunol 2022; 13:903758. [PMID: 36016939 PMCID: PMC9395983 DOI: 10.3389/fimmu.2022.903758] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 07/21/2022] [Indexed: 11/30/2022] Open
Abstract
Ferroptosis is a more relatively recently identified type of programmed cell death, which is associated with tumor progression. However, the mechanism underlying the effect of ferroptosis-related long non-coding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) remains elusive. Therefore, the current study aimed to investigate the role of ferroptosis-related lncRNAs in LUAD and to develop a prognostic model. The clinicopathological characteristics of patients and the gene sequencing data were obtained from The Cancer Genome Atlas, while the ferroptosis-associated mRNAs were downloaded from the FerrDb database. A ferroptosis-related lncRNA signature was established with Least Absolute Shrinkage and Selection Operator Cox regression analysis. Furthermore, the risk scores of ferroptosis-related lncRNAs were calculated and LUAD patients were then assigned to high- and low-risk groups based on the median risk score. The prognostic model was established by K-M plotters and nomograms. Gene set enrichment analysis (GSEA) was performed to evaluate the association between immune responses and ferroptosis-related lncRNAs. A total of 10 ferroptosis-related lncRNAs were identified as independent predictors of LUAD outcome, namely RP11-386M24.3, LINC00592, FENDRR, AC104699.1, AC091132.1, LANCL1-AS1, LINC-PINT, IFNG-AS1, LINC00968 and AC006129.2. The area under the curve verified that the established signatures could determine LUAD prognosis. The nomogram model was used to assess the predictive accuracy of the established signatures. Additionally, GSEA revealed that the 10 ferroptosis-related lncRNAs could be involved in immune responses in LUAD. Overall, the results of the current study may provide novel insights into the development of novel therapies or diagnostic strategies for LUAD.
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Affiliation(s)
- Yuanyong Wang
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Guofang Lu
- Department of Physiology and Pathophysiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi’an, China
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Xinying Xue
- Department of Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, China
- Department of Respiratory Disease, School of Clinical Medicine, Weifang Medical University, Weifang, China
- Department of Respiratory and Critical Care, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Mei Xie
- Department of Respiratory and Critical Care, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Zhaoyang Wang
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Zhiqiang Ma
- Department of Oncology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yingtong Feng
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Changjian Shao
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Hongtao Duan
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Minghong Pan
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Peng Ding
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
| | - Xiaofei Li
- Department of Thoracic Surgery, Xi’an International Medical Center Hospital, Xi’an, China
- *Correspondence: Xiaolong Yan, ; Jing Han, hanjing.cn.@163.com; Xiaofei Li,
| | - Jing Han
- Department of Ophthalmology, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
- *Correspondence: Xiaolong Yan, ; Jing Han, hanjing.cn.@163.com; Xiaofei Li,
| | - Xiaolong Yan
- Department of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi’an, China
- *Correspondence: Xiaolong Yan, ; Jing Han, hanjing.cn.@163.com; Xiaofei Li,
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Novel Prognosis and Therapeutic Response Model of Immune-Related lncRNA Pairs in Clear Cell Renal Cell Carcinoma. Vaccines (Basel) 2022; 10:vaccines10071161. [PMID: 35891325 PMCID: PMC9325030 DOI: 10.3390/vaccines10071161] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/11/2022] [Accepted: 07/15/2022] [Indexed: 01/13/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common type of renal carcinoma. It is particularly important to accurately judge the prognosis of patients. Since most tumor prediction models depend on the specific expression level of related genes, a better model therefore needs to be constructed. To provide an immune-related lncRNA (irlncRNAs) tumor prognosis model that is independent of the specific gene expression levels, we first downloaded and sorted out the data on ccRCC in the TCGA database and screened irlncRNAs using co-expression analysis and then obtained the differently expressed irlncRNA (DEirlncRNA) pairs by means of univariate analysis. In addition, we modified LASSO penalized regression. Subsequently, the ROC curve was drawn, and we compared the area under the curve, calculated the Akaike information standard value of the 5-year receiver operating characteristic curve, and determined the cut-off point to establish the best model to distinguish the high- or low-disease-risk group of ccRCC. Subsequently, we reassessed the model from the perspectives of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutics efficacy, and immunosuppressed biomarkers. A total of 17 DEirlncRNAs pairs (AL031710.1|AC104984.5, AC020907.4|AC127-24.4,AC091185.1|AC005104.1, AL513218.1|AC079015.1, AC104564.3|HOXB-AS3, AC003070.1|LINC01355, SEMA6A-AS1|CR936218.1, AL513327.1|AS005785.1, AC084876.1|AC009704.2, IGFL2-AS1|PRDM16-DT, AC011462.4|MMP25-AS1, AL662844.3I|TGB2-AS1, ARHGAP27P1|AC116914.2, AC093788.1|AC007098.1, MCF2L-AS1|AC093001.1, SMIM25|AC008870.2, and AC027796.4|LINC00893) were identified, all of which were included in the Cox regression model. Using the cut-off point, we can better distinguish patients according to different factors, such as survival status, invasive clinic-pathological features, tumor immune infiltration, whether they are sensitive to chemotherapy or not, and expression of immunosuppressive biomarkers. We constructed the irlncRNA model by means of pairing, which can better eliminate the dependence on the expression level of the target genes. In other words, the signature established by pairing irlncRNA regardless of expression levels showed promising clinical prediction value.
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Zhi S, Yang B, Zhou S, Tan J, Zhong G, Han F. Immune-Related LncRNAs to Construct a Prognosis Risk-Assessment Model for Gastric Cancer. Curr Oncol 2022; 29:4923-4935. [PMID: 35877251 PMCID: PMC9318354 DOI: 10.3390/curroncol29070391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/01/2022] [Accepted: 07/09/2022] [Indexed: 01/03/2023] Open
Abstract
Background: Gastric cancer is a prevalent cause of tumor death. Tumor immunotherapy aims to reshape the specific immunity to tumors in order to kill the tumor. LncRNAs play a pivotal role in regulating the tumor immune microenvironment. Herein, immune-related lncRNAs were used to establish a prognosis risk-assessment model for gastric cancer and provide personalized predictions while providing insights and targets for gastric cancer treatment to enhance patient prognosis. Methods: Gastric adenocarcinoma transcriptome and clinical data were acquired from the The Cancer Genome Atlas (TCGA) database to screen the immune-related lncRNAs. Then, LASSO COX regression was utilized to construct the prognosis risk-assessment model. Afterward, the reliability of the model was evaluated the relationship between immune infiltration, clinical characteristics, and the model was analyzed. Results: We identified 13 lncRNAs and constructed the prognosis assessment model. According to the median risk score of the training set, the patients were assigned to different risk groups. Overall survival time was shorter in the high-risk group. In the high-risk group, higher infiltration of mono-macrophages, dendritic cells, CD4+ T cells, and CD8+ T cells was observed. Moreover, the model was positively related to tumor metastasis. Conclusion: The prognosis risk-assessment model developed in this research can effectively predict the prognosis of gastric cancer patients. This tool is expected to be further applied to clinics in the future, thus providing a novel target for immunotherapy in gastric cancer patients.
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Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney. DISEASE MARKERS 2022; 2022:4752184. [PMID: 35756490 PMCID: PMC9217527 DOI: 10.1155/2022/4752184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 05/10/2022] [Accepted: 05/25/2022] [Indexed: 11/17/2022]
Abstract
Background Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis. Methods We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis. Results A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients (p < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, p value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, p value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients. Conclusions The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.
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Tian J, Fu C, Zeng X, Fan X, Wu Y. An Independent Prognostic Model Based on Ten Autophagy-Related Long Noncoding RNAs in Pancreatic Cancer Patients. Genet Res (Camb) 2022; 2022:3895396. [PMID: 35645615 PMCID: PMC9124146 DOI: 10.1155/2022/3895396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 04/27/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose Pancreatic cancer (PC) is a common, highly lethal cancer with a low survival rate. Autophagy is involved in the occurrence and progression of PC. This study aims to explore the feasibility of using an autophagy-related long noncoding RNA (lncRNA) signature for assessing PC patient survival. Methods We obtained RNA sequencing and clinical data of patients from the TCGA website. Autophagy genes were obtained from the Human Autophagy Database. The prognostic model, generated through univariate and multivariate Cox regression analyses, included 10 autophagy-related lncRNAs. Receiver operating characteristic (ROC) curves and forest plots were generated for univariate and multivariate Cox regression analyses, to examine the predictive feasibility of the risk model. Gene set enrichment analysis (GSEA) was used to screen enriched gene sets. Results Twenty-eight autophagy-related lncRNAs were filtered out through univariate Cox regression analysis (P < 0.001). Ten autophagy-related lncRNAs, including 4 poor prognosis factors and 6 beneficial prognosis factors, were further screened via multivariate Cox regression analysis. The AUC value of the ROC curve was 0.815. GSEA results demonstrated that cancer-related gene sets were significantly enriched. Conclusion A signature based on ten autophagy-related lncRNAs was identified. This signature could be potentially used for evaluating clinical prognosis and might be used for targeted therapy against PC.
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Affiliation(s)
- Jiahui Tian
- Department of Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, China
- Department of Medicine, Hunan Normal University, Changsha, Hunan 410005, China
| | - Chunyan Fu
- Department of Medicine, Hunan Normal University, Changsha, Hunan 410005, China
| | - Xuan Zeng
- Department of Medicine, Hunan Normal University, Changsha, Hunan 410005, China
| | - Xiaoxiao Fan
- Department of Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, China
| | - Yi Wu
- Department of Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, China
- Department of Medicine, Hunan Normal University, Changsha, Hunan 410005, China
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Zhou M, Wu T, Yuan Y, Dong SJ, Zhang ZM, Wang Y, Wang J. A risk score system based on a six-microRNA signature predicts the overall survival of patients with ovarian cancer. J Ovarian Res 2022; 15:54. [PMID: 35513874 PMCID: PMC9074233 DOI: 10.1186/s13048-022-00980-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/12/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Ovarian cancer (OVC) is a devastating disease worldwide; therefore the identification of prognostic biomarkers is urgently needed. We aimed to determine a robust microRNA signature-based risk score system that could predict the overall survival (OS) of patients with OVC. METHODS We extracted the microRNA expression profiles and corresponding clinical data of 467 OVC patients from The Cancer Genome Atlas (TCGA) database and further divided this data into training, validation and complete cohorts. The key prognostic microRNAs for OVC were identified and evaluated by robust likelihood-based survival analysis (RLSA) and multivariable Cox regression. Time-dependent receiver operating characteristic (ROC) curves were then constructed to evaluate the prognostic performance of these microRNAs. A total of 172 ovarian cancer samples and 162 normal ovarian tissues were used to verify the credibility and accuracy of the selected markers of the TCGA cohort by quantitative real-time polymerase chain reaction (PCR). RESULTS We successfully established a risk score system based on a six-microRNA signature (hsa-miR-3074-5p, hsa-miR-758-3p, hsa-miR-877-5p, hsa-miR-760, hsa-miR-342-5p, and hsa-miR-6509-5p). This microRNA based system is able to characterize patients as either high or low risk. The OS of OVC patients, with either high or low risk, was significantly different when compared in the training cohort (p < 0.001), the validation cohort (p < 0.001) and the complete cohort (p < 0.001). Analysis of clinical samples further demonstrated that these microRNAs were aberrantly expressed in OVC tissues. The six-miRNA-based signature was correlated with the prognosis of OVC patients (p < 0.001). CONCLUSIONS The study established a novel risk score system that is predictive of patient prognosis and is a potentially useful guide for the personalized treatment of OVC patients.
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Affiliation(s)
- Min Zhou
- Department of Gynecologic Cancer, Shaanxi Provincial Cancer Hospital, No. 309 Yanta West Road, Shaanxi, 710061, Xi'an, People's Republic of China
| | - Tao Wu
- Department of Gynecologic Cancer, Shaanxi Provincial Cancer Hospital, No. 309 Yanta West Road, Shaanxi, 710061, Xi'an, People's Republic of China
| | - Yuan Yuan
- Department of Gynecologic Cancer, Shaanxi Provincial Cancer Hospital, No. 309 Yanta West Road, Shaanxi, 710061, Xi'an, People's Republic of China
| | - Shu-Juan Dong
- Department of Obstetrics and Gynecology, Shaanxi Provincial Rehabilitation Hospital, Xi'an, Shaanxi, People's Republic of China
| | - Zhi-Ming Zhang
- Department of Clinical Laboratory, Xi'an Central Hospital, Xi'an, Shaanxi, People's Republic of China
| | - Yan Wang
- Department of Gynecology, Xi'an Central Hospital, No.161 five West Road, Xi'an, Shaanxi, People's Republic of China.
| | - Jing Wang
- Department of Gynecologic Cancer, Shaanxi Provincial Cancer Hospital, No. 309 Yanta West Road, Shaanxi, 710061, Xi'an, People's Republic of China.
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Tan Y, Lu L, Liang X, Chen Y. Identification of a pyroptosis-related lncRNA risk model for predicting prognosis and immune response in colon adenocarcinoma. World J Surg Oncol 2022; 20:118. [PMID: 35413978 PMCID: PMC9004096 DOI: 10.1186/s12957-022-02572-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 03/17/2022] [Indexed: 12/12/2022] Open
Abstract
Background Colon adenocarcinoma (COAD) is one of the most common malignant tumors and is diagnosed at an advanced stage with a poor prognosis worldwide. Pyroptosis is involved in the initiation and progression of tumors. This research focused on constructing a pyroptosis-related ceRNA network to generate a reliable risk model for risk prediction and immune infiltration analysis of COAD. Methods Transcriptome data, miRNA-sequencing data, and clinical information were downloaded from the TCGA database. First, differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) were identified to construct a pyroptosis-related ceRNA network. Second, a pyroptosis-related lncRNA risk model was developed applying univariate Cox regression analysis and least absolute shrinkage and selection operator method (LASSO) regression analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were utilized to functionally annotate RNAs contained in the ceRNA network. In addition, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox regression, and nomogram were applied to validate this risk model. Finally, the relationship of this risk model with immune cells and immune checkpoint blockade (ICB)-related genes was analyzed. Results A total of 5373 DEmRNAs, 1159 DElncRNAs, and 355 DEmiRNAs were identified. A pyroptosis-related ceRNA regulatory network containing 132 lncRNAs, 7 miRNAs, and 5 mRNAs was constructed, and a ceRNA-based pyroptosis-related risk model including 11 lncRNAs was built. The tumor tissues were classified into high- and low-risk groups according to the median risk score. Kaplan-Meier analysis showed that the high-risk group had a shorter survival time; ROC analysis, independent prognostic analysis, and nomogram further indicated the risk model was a significant independent prognostic factor what had an excellent ability to predict patients’ risk. Moreover, immune infiltration analysis indicated that the risk model was related to immune infiltration cells (i.e., B cell naïve, T cell follicular helper, macrophage M1) and ICB-related genes (i.e., PD-1, CTLA4, HAVCR2). Conclusions This pyroptosis-related lncRNA risk model possessed good prognostic value, and the ability to predict the outcome of ICB immunotherapy in COAD. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02572-8.
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Affiliation(s)
- Yuying Tan
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China
| | - Liqing Lu
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China
| | - Xujun Liang
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China.
| | - Yongheng Chen
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China. .,National Clinical Research Center for Geriatric Disorders, XiangYa Hospital, Central South University, Changsha, 410008, China.
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Liu S, Peng X, Wu X, Bu F, Yu Z, Zhu J, Luo C, Zhang W, Liu J, Huang J. Construction of a new immune-related lncRNA model and prediction of treatment and survival prognosis of human colon cancer. World J Surg Oncol 2022; 20:71. [PMID: 35249533 PMCID: PMC8900415 DOI: 10.1186/s12957-022-02508-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 01/20/2022] [Indexed: 12/24/2022] Open
Abstract
Background An increasing number of studies have shown that immune-related long noncoding RNAs (lncRNAs) do not require a unique expression level. This finding may help predict the survival and drug sensitivity of patients with colon cancer. Methods We retrieved original transcriptome and clinical data from The Cancer Genome Atlas (TCGA), sorted the data, differentiated mRNAs and lncRNAs, and then downloaded immune-related genes. Coexpression analysis predicted immune-related lncRNAs (irlncRNAs) and univariate analysis identified differentially expressed irlncRNAs (DEirlncRNAs). We have also amended the lasso pending region. Next, we compared the areas under the curve (AUCs), counted the Akaike information standard (AIC) value of the 3-year receiver operating characteristic (ROC) curve, and determined the cutoff point to establish the best model to differentiate the high or low disease risk group of colon cancer patients. Results We reevaluated the patients regarding the survival rate, clinicopathological features, tumor-infiltrating immune cells, immunosuppressive biomarkers, and chemosensitivity. A total of 155 irlncRNA pairs were confirmed, 31 of which were involved in the Cox regression model. After the colon cancer patients were regrouped according to the cutoff point, we could better distinguish the patients based on adverse survival outcomes, invasive clinicopathological features, the specific tumor immune cell infiltration status, high expression of immunosuppressive biomarkers, and low chemosensitivity. Conclusions In this study, we established a characteristic model by pairing irlncRNAs to better predict the survival rate, chemotherapy efficacy, and prognostic value of patients with colon cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02508-2.
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Li J, Zhang J, Tao S, Hong J, Zhang Y, Chen W. Prognostication of Pancreatic Cancer Using The Cancer Genome Atlas Based Ferroptosis-Related Long Non-Coding RNAs. Front Genet 2022; 13:838021. [PMID: 35237306 PMCID: PMC8883032 DOI: 10.3389/fgene.2022.838021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 01/18/2022] [Indexed: 12/20/2022] Open
Abstract
Background: Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical. Methods: In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed. Results: Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction. Conclusion: The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.
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Affiliation(s)
- Jiayu Li
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jinghui Zhang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuiliang Tao
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiaze Hong
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuyan Zhang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Yuyan Zhang, ; Weiyan Chen,
| | - Weiyan Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
- *Correspondence: Yuyan Zhang, ; Weiyan Chen,
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Tang R, Wu Z, Rong Z, Xu J, Wang W, Zhang B, Yu X, Shi S. Ferroptosis-related lncRNA pairs to predict the clinical outcome and molecular characteristics of pancreatic ductal adenocarcinoma. Brief Bioinform 2022; 23:bbab388. [PMID: 34553745 DOI: 10.1093/bib/bbab388] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 08/13/2021] [Accepted: 08/28/2021] [Indexed: 01/20/2023] Open
Abstract
Ferroptosis is a form of regulated cell death initiated by oxidative perturbations that can be blocked by iron chelators and lipophilic antioxidants, and ferroptosis may be the silver bullet treatment for multiple cancers, including immunotherapy- and chemotherapy-insensitive cancers such as pancreatic ductal adenocarcinoma (PDAC). Numerous studies have noted that long non-coding RNAs (lncRNAs) regulate the biological behaviour of cancer cells by binding to DNA, RNA and protein. However, few studies have reported the role of lncRNAs in ferroptosis processes and the function of ferroptosis-associated lncRNAs. The primary objective of the present study was to identify ferroptosis-related lncRNAs using bioinformatic approaches combined with experimental validation. The second objective was to construct a prognostic model to predict the overall survival of patients with PDAC. The present study identified ferroptosis-related lncRNAs using a bioinformatic approach and validated them in an independent pancreatic cancer cohort from Fudan University Shanghai Cancer Center. The lncRNA SLCO4A1-AS1 was identified as a novel molecule mediating ferroptosis resistance in vitro. A novel algorithm was used to construct a '0 or 1' matrix-based prognosis model, which showed promising diagnostic accuracy for potential clinical translation (area under the curve = 0.89 for the 2-year survival rate). Notably, molecular subtypes classified by the risk scores of the model did not belong to any previously reported subtypes of PDAC. The immune microenvironment, metabolic activities, mutation landscape and ferroptosis sensitivity were significantly distinct between patients with different risk scores. Sensitivity (IC50) to 30 common anticancer drugs was analysed between patients with different risks, and imatinib and axitinib were found to be potential drugs for the treatment of patients with lower risk scores. Overall, we developed an accurate prognostic model based on the expression patterns of ferroptosis lncRNAs, which may contribute greatly to the evaluation of patient prognosis, molecular characteristics and treatment modalities and could be further translated into clinical applications.
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Affiliation(s)
- Rong Tang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zijian Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zeyin Rong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Zhang Z, Luo Y, Zhang C, Wu P, Zhang G, Zeng Q, Wang L, Xue L, Yang Z, Zeng H, Zheng B, Tan F, Xue Q, Gao S, Sun N, He J. An immune-related lncRNA signature predicts prognosis and adjuvant chemotherapeutic response in patients with small-cell lung cancer. Cancer Cell Int 2021; 21:691. [PMID: 34930244 PMCID: PMC8691030 DOI: 10.1186/s12935-021-02357-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/22/2021] [Indexed: 11/23/2022] Open
Abstract
Background Patients with small-cell lung cancer (SCLC) are burdened by limited treatment options and the disease’s dismal prognosis. Long non-coding RNAs (lncRNAs) are essential regulators of genetic alteration and are actively involved in tumor immunity. However, few studies have examined interactions between immune genes and lncRNAs in SCLC. Methods Immune-related lncRNA (irlncRNA) expression profiles and their clinical significance were explored. We enrolled 227 patients with SCLC, including 79 cases from GSE65002 and 148 cases from a validation cohort with corresponding qPCR data. The least absolute shrinkage and selection operator (LASSO) model was applied to identify prognostic irlncRNAs for an irlncRNA-based SCLC signature. We additionally investigated the potential mechanisms and immune landscape of the signature using bioinformatics methods. Results An irlncRNA signature including 8 irlncRNAs (ENOX1-AS1, AC005162, LINC00092, RPL34-AS1, AC104135, AC015971, AC126544, AP001189) was established for patients with SCLC in the training cohort. Low-risk patients were more likely to benefit from chemotherapy and achieve a favorable prognosis. The signature was also well-validated in the validation cohort and various clinical subgroups. Compared to other clinical parameters, the irlncRNA signature exhibited superior predictive performance for chemotherapy response and prognosis. The signature was as an independent prognostic factor in the training and validation cohorts. Interestingly, low-risk patients showed an activated immune phenotype. Conclusion We constructed the first irlncRNA-based signature for chemotherapy efficacy and outcome prediction. The irlncRNA signature is a reliable and robust prognostic classifier that could be useful for clinical management and determination of potential chemotherapy benefit for patients with SCLC. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02357-1.
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Lin Y, Pan X, Chen Z, Lin S, Shen Z, Chen S. Prognostic value and immune infiltration of novel signatures in colon cancer microenvironment. Cancer Cell Int 2021; 21:679. [PMID: 34922547 PMCID: PMC8684099 DOI: 10.1186/s12935-021-02342-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 11/15/2021] [Indexed: 12/16/2022] Open
Abstract
Background Growing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding RNAs (lncRNAs) related to immune microenvironment (IM) in colon cancer. Methods Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncRNA signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content. Results Colon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncRNA signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages. Conclusion The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02342-8.
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Affiliation(s)
- Yilin Lin
- Department of Gastroenterological Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng, Beijing, China
| | - Xiaoxian Pan
- Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Zhihua Chen
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang, Fuzhou, Fujian, China
| | - Suyong Lin
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang, Fuzhou, Fujian, China
| | - Zhanlong Shen
- Department of Gastroenterological Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng, Beijing, China.
| | - Shaoqin Chen
- Department of Gastroenterological Surgery, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang, Fuzhou, Fujian, China.
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Yuan H, Liu J, Zhao L, Wu P, Chen G, Chen Q, Shen P, Yang T, Fan S, Xiao B, Jiang K. Prognostic Risk Model and Tumor Immune Environment Modulation of m5C-Related LncRNAs in Pancreatic Ductal Adenocarcinoma. Front Immunol 2021; 12:800268. [PMID: 34956238 PMCID: PMC8692582 DOI: 10.3389/fimmu.2021.800268] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/19/2021] [Indexed: 11/13/2022] Open
Abstract
RNA methylation modification is a key process in epigenetics that regulates posttranscriptional gene expression. With advances in next-generation sequencing technology, 5-methylcytosine (m5C) modification has also been found in multiple RNAs. Long non-coding RNAs (lncRNAs) were proved to have a key role in cancer progression and closely related to the tumor immune microenvironment. Thus, based on the PDAC patients' clinical information and genetic transcriptome data from the TCGA database, we performed a detailed bioinformatic analysis to establish a m5C-related lncRNA prognostic risk model for PDAC patients and discovered the relationship between the risk model and PDAC immune microenvironment. Pearson correlation coefficient analysis was applied to conduct a m5C regulatory gene and m5C-related lncRNA co-expression network. Expression of m5C-related lncRNAs screened by univariate regression analysis with prognostic value showed a significant difference between pancreatic cancer and normal tissues. The least absolute shrinkage and selection operator (LASSO) Cox regression method was applied to determine an 8-m5C-related lncRNA prognostic risk model. We used principal component analysis to indicate that the risk model could distinguish all the samples clearly. The clinical nomogram also accurately predicted 1-, 1.5-, 2-, and 3-year survival time among PDAC patients. Additionally, this risk model was validated in the entire group and sub-test groups using KM analysis and ROC analysis. Combined with the clinical characteristics, the risk score was found to be an independent factor for predicting the survival of PDAC patients. Furthermore, the association between the risk model and tumor immune microenvironment was evaluated via the ESTIMATE R package and CIBERSORT method. Consequently, the results indicated that immune cells were associated with m5C-related lncRNA risk model scores and had different distribution in the high- and low-risk groups. Based on all these analyses, the m5C-related lncRNA risk model could be a reliable prognostic tool and therapeutic target for PDAC patients.
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Affiliation(s)
- Hao Yuan
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Jinhui Liu
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li Zhao
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Pengfei Wu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Guosheng Chen
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Qun Chen
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Peng Shen
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Taoyue Yang
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Shaoqing Fan
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Bin Xiao
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
| | - Kuirong Jiang
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
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Dai S, Yao D. An immune-associated ten-long noncoding RNA signature for predicting overall survival in cervical cancer. Transl Cancer Res 2021; 10:5295-5306. [PMID: 35116378 PMCID: PMC8799008 DOI: 10.21037/tcr-21-2390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/25/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Several immune-associated long non-coding RNA (lncRNA) signatures have been reported as prognostic models in different types of cancers; however, the immune-associated lncRNA signature for predicting overall survival (OS) in cervical cancer is unknown. METHODS The lncRNA expression profiles and clinical data of cervical cancer were acquired from The Cancer Genome Atlas (TCGA) dataset. Immune-associated genes were extracted from the Molecular Signatures Database (MSigDB), and the immune-associated lncRNAs were extracted for Cox regression analysis. Principal component analysis (PCA) was used to distinguish the high and low risk status of cervical cancer patients. Gene Set Enrichment Analysis (GSEA) was used for functional analyses. RESULTS Cox regression analyses and the least absolute shrinkage and selection operator (LASSO) Cox regression model were used to construct an immune-associated ten-lncRNA signature (containing AL021807.1, AL109976.1, LINC02446, MIR4458HG, AC004540.2, AC009065.8, AC083809.1, AC055822.1, AP000904.1, and FBXL19-AS1) for predicting OS in cervical cancer. The signature segregated the cervical cancer patients into 2 groups (high-risk group and low-risk group). The Kaplan-Meier survival curves of AL021807.1, AL109976.1, LINC02446, and MIR4458HG were statistically significant (P<0.05) and the others (including AC004540.2, AC009065.8, AC083809.1, AC055822.1, AP000904.1, and FBXL19-AS1) were not statistically significant (P>0.05). The Kaplan-Meier survival curves of the signature were statistically significant (P=1.134e-10), and the 5-year survival rate was 0.444 in the high-risk group [95% confidence interval (CI): 0.334 to 0.590] and 0.884 in the low-risk group (95% CI: 0.807 to 0.969). The area under curve (AUC) of the receiver operating characteristic (ROC) curve of the signature was 0.833. The concordance index (C-index) of the signature was 0.788 (95% CI: 0.730 to 0.846, P=1.884778e-22). The PCA successfully distinguished the high-risk group and low-risk group based on the signature. The GSEA showed that the signature-related protein coding genes (PCGs) may participate in immunologic biological processes and pathways. CONCLUSIONS This study revealed that the immune-associated ten-lncRNA signature is an independent factor for cervical cancer prognosis prediction, providing a bright future for immunotherapy of cervical cancer patients.
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Affiliation(s)
- Shengkang Dai
- Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
- People’s Hospital of Baise, Baise, China
| | - Desheng Yao
- Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
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Lei Y, Tang R, Xu J, Zhang B, Liu J, Liang C, Meng Q, Hua J, Yu X, Wang W, Shi S. Construction of a novel risk model based on the random forest algorithm to distinguish pancreatic cancers with different prognoses and immune microenvironment features. Bioengineered 2021; 12:3593-3602. [PMID: 34238114 PMCID: PMC8806465 DOI: 10.1080/21655979.2021.1951527] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 06/26/2021] [Indexed: 12/16/2022] Open
Abstract
Immune-related long noncoding RNAs (irlncRNAs) are actively involved in regulating the immune status. This study aimed to establish a risk model of irlncRNAs and further investigate the roles of irlncRNAs in predicting prognosis and the immune landscape in pancreatic cancer. The transcriptome profiles and clinical information of 176 pancreatic cancer patients were retrieved from The Cancer Genome Atlas (TCGA). Immune-related genes (irgenes) downloaded from ImmPort were used to screen 1903 immune-related lncRNAs (irlncRNAs) using Pearson's correlation analysis (R > 0.5; p < 0.001). Random survival forest (RSF) and survival tree analysis showed that 9 irlncRNAs were highly correlated with overall survival (OS) according to the variable importance (VIMP) and minimal depth. Next, Cox regression analysis was used to establish a risk model with 3 irlncRNAs (LINC00462, LINC01887, RP11-706C16.8) that was evaluated by Kaplan-Meier analysis, the areas under the curve (AUCs) of the receiver operating characteristics and the C-index. Additionally, we performed Cox regression analysis to establish the clinical prognostic model, which showed that the risk score was an independent prognostic factor (p < 0.001). A nomogram and calibration plots were drawn to visualize the clinical features. The Wilcoxon signed-rank test and Pearson's correlation analysis further explored the irlncRNA signatures and immune cell infiltration, as well as the immunotherapy response.
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Affiliation(s)
- Yalan Lei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Rong Tang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Liu LP, Lu L, Zhao QQ, Kou QJ, Jiang ZZ, Gui R, Luo YW, Zhao QY. Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning. Front Cell Dev Biol 2021; 9:756340. [PMID: 34805165 PMCID: PMC8599430 DOI: 10.3389/fcell.2021.756340] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 10/04/2021] [Indexed: 12/20/2022] Open
Abstract
Lung cancer remains the leading cause of cancer death globally, with lung adenocarcinoma (LUAD) being its most prevalent subtype. Due to the heterogeneity of LUAD, patients given the same treatment regimen may have different responses and clinical outcomes. Therefore, identifying new subtypes of LUAD is important for predicting prognosis and providing personalized treatment for patients. Pyroptosis-related genes play an essential role in anticancer, but there is limited research investigating pyroptosis in LUAD. In this study, 33 pyroptosis gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. By bioinformatics and machine learning analyses, we identified novel subtypes of LUAD based on 10 pyroptosis-related genes and further validated them in the GEO dataset, with machine learning models performing up to an AUC of 1 for classifying in GEO. A web-based tool was established for clinicians to use our clustering model (http://www.aimedicallab.com/tool/aiml-subphe-luad.html). LUAD patients were clustered into 3 subtypes (A, B, and C), and survival analysis showed that B had the best survival outcome and C had the worst survival outcome. The relationships between pyroptosis gene expression and clinical characteristics were further analyzed in the three molecular subtypes. Immune profiling revealed significant differences in immune cell infiltration among the three molecular subtypes. GO enrichment and KEGG pathway analyses were performed based on the differential genes of the three subtypes, indicating that differentially expressed genes (DEGs) were involved in multiple cellular and biological functions, including RNA catabolic process, mRNA catabolic process, and pathways of neurodegeneration-multiple diseases. Finally, we developed an 8-gene prognostic model that accurately predicted 1-, 3-, and 5-year overall survival. In conclusion, pyroptosis-related genes may play a critical role in LUAD, and provide new insights into the underlying mechanisms of LUAD.
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Affiliation(s)
- Le-Ping Liu
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Lu Lu
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qiang-Qiang Zhao
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qin-Jie Kou
- Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Zhen-Zhen Jiang
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Rong Gui
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yan-Wei Luo
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qin-Yu Zhao
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China.,College of Engineering and Computer Science, The Australian National University, Canberra, ACT, Australia
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Ma E, Hou S, Wang Y, Xu X, Wang Z, Zhao J. Identification and Validation of an Immune-Related lncRNA Signature to Facilitate Survival Prediction in Gastric Cancer. Front Oncol 2021; 11:666064. [PMID: 34760687 PMCID: PMC8573392 DOI: 10.3389/fonc.2021.666064] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 10/06/2021] [Indexed: 12/27/2022] Open
Abstract
Background Long noncoding RNAs (lncRNAs) are versatile in functions and can regulate cancer development, including the modulation of cancer immunity. Immune-related lncRNA signatures predicting prognosis have been reported in multiple cancers, but relevant studies in gastric cancer (GC) are still lacking. Methods We performed a comprehensive analysis using TCGA and Immport databases and identified an immune-related lncRNA signature by univariate and multivariate Cox regression analysis. qRT-PCR and immunohistochemistry assays were used for further validation. KEGG and GO analysis and ceRNA network establishment were carried out to explore the regulatory functions. Results We first identified an immune-related lncRNA signature, which can stratify gastric cancer patients into high- and low-risk subgroups and the high-risk cases frequently suffered from shorter overall survival time. Next, we validated the reliability of the lncRNA signature in an independent 75 gastric cancer samples and demonstrated that the three-year survival rate in high-risk patients was only 30.8% versus 66.5% in low-risk counterparts. Functional exploration indicated that the lncRNA signature might participate in multiple cancer-associated processes including cell adhesion and migration, cytokine-receptor interaction and immune evasion. Additionally, we observed that high-risk samples tended to form an immunosuppressive microenvironment, which had more M2-polarized macrophages and Tregs, but fewer CD8 effector T cells within tumors. Moreover, we found that PD-1 and PD-L1 were dramatically upregulated in a subset of high-risk patients with abundant M2 and Treg infiltration, implying these patients may benefit from anti-PD-1 and PD-L1 immunotherapy. Conclusions These results showed that the immune-related lncRNA signature had a prominent capacity to predict overall survival and the immune status of microenvironment in gastric cancer. Our findings may be useful for the risk-stratification management and provide a valuable clue to identify proper patients potentially benefit from immune checkpoint therapy in gastric cancer.
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Affiliation(s)
- Ensi Ma
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institute of Organ Transplantation, Fudan University, Shanghai, China
| | - Sen Hou
- Department of Digestive Surgery, Xuchang Central Hospital, Henan, China
| | - Yan Wang
- Central Laboratory, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiao Xu
- Central Laboratory, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhengxin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institute of Organ Transplantation, Fudan University, Shanghai, China
| | - Jing Zhao
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Cancer Metastasis Institute, Fudan University, Shanghai, China
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Liu J, Zheng Z, Zhang W, Wan M, Ma W, Wang R, Yan Y, Guo Y, Zhang J, Li W, Yao X. Dysregulation of tumor microenvironment promotes malignant progression and predicts risk of metastasis in bladder cancer. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1438. [PMID: 34733990 PMCID: PMC8506754 DOI: 10.21037/atm-21-4023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/02/2021] [Indexed: 11/12/2022]
Abstract
Background The tumor microenvironment (TME) is not only a key factor in the malignant progression of cancer but also plays an indispensable role in tumor immunotherapy. As an important regulatory factor in the TME, long non-coding RNAs (incRNA) are important for the development of bladder cancer. The purpose of this study was to explore the molecular mechanism of malignant progression of bladder cancer (BCa) from the perspective of immunology, establish a reliable signature, and evaluate its effect on prognosis, metastasis, and the effectiveness of immunotherapy. Methods The TME was assessed by single-sample gene set enrichment analysis (ssGSEA) in 373 patients with muscle invasive bladder cancer (MIBC) in The Cancer Genome Atlas (TCGA). Combining RNA sequence data from 49 BCa patients in our center, we established TME-related prognostic signatures (TMERPS) based on TME-related immune prognosis genes using weighted gene correlation network analysis, selection operator Cox analysis, minimum absolute shrinkage, and survival analysis. Real-Time Quantitative PCR was used for expression level analysis of related genes. Functional enrichment analysis and nomograms were used to explore the potential impact of TMERPS on the immune system, prognosis, and metastasis. Results The ssGSEA proved to be an accurate assessment of immune levels in BCa samples. TMERPS was established based on six TME-associated prognostic lncRNAs and was shown to be closely associated with prognosis, metastasis, and immune levels, and to have a significant stratifying effect on the therapeutic efficacy of immune checkpoint inhibitors. Finally, three TMERPS-based nomograms were shown to be effective in predicting prognosis, lymph node metastasis, and distant metastasis in BCa patients. Conclusions TMERPS can stratify BCa patients into different risk groups with different prognoses, immunotherapy sensitivity, and risk of metastasis. TMERPS-based nomograms can effectively predict prognosis and metastasis in BCa patients.
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Affiliation(s)
- Ji Liu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Zongtai Zheng
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Wentao Zhang
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Moxi Wan
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Wenchao Ma
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Ruiliang Wang
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Yang Yan
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Yadong Guo
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Junfeng Zhang
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Wei Li
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
| | - Xudong Yao
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.,Institute of Urinary Oncology, School of Medicine, Tongji University, Shanghai, China
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Pei G, Ma N, Chen F, Guo L, Bai J, Deng J, He Z. Screening and Identification of Hub Genes in the Corticosteroid Resistance Network in Human Airway Epithelial Cells via Microarray Analysis. Front Pharmacol 2021; 12:672065. [PMID: 34707493 PMCID: PMC8542788 DOI: 10.3389/fphar.2021.672065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 09/27/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Objective: Corticosteroid resistance is a major barrier to chronic obstructive pulmonary disease (COPD), but the exact mechanism of corticosteroid resistance in COPD has been less well studied. Methods: The microarray dataset GSE11906, which includes genomic and clinical data on COPD, was downloaded from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified using R software. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes (KEGG) were utilized to enrich and analyze the gene cohort related to the response to steroid hormones, respectively. The Connectivity Map (CMap) database was used to screen corticosteroid resistance-related drugs that might exert a potential therapeutic effect. STRING was used to construct a protein-protein interaction (PPI) network of the gene cohort, and the CytoHubba plug-in of Cytoscape was used to screen the hub genes in the PPI network. The expression levels of hub genes in cigarette smoke extract (CSE)-stimulated bronchial epithelial cells were assayed by quantitative real-time PCR and western blotting. Results: Twenty-one genes were found to be correlated with the response to steroid hormones. In the CMap database, 32 small-molecule compounds that might exert a therapeutic effect on corticosteroid resistance in COPD were identified. Nine hub genes were extracted from the PPI network. The expression levels of the BMP4, FOS, FN1, EGFR, and SPP1 proteins were consistent with the microarray data obtained from molecular biology experiments. Scopoletin significantly restrained the increases in the levels of AKR1C3, ALDH3A1, FN1 and reversed the decreases of phosphorylated GR and HDAC2 caused by CSE exposure. Conclusion: The BMP4, FOS, FN1, EGFR, and SPP1 genes are closely correlated with CSE-induced glucocorticoid resistance in airway epithelial cells. Scopoletin may be a potential drug for the treatment of glucocorticoid resistance caused by CSE.
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Affiliation(s)
- Guangsheng Pei
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
| | - Nan Ma
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Fugang Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Liyan Guo
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jing Bai
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jingmin Deng
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhiyi He
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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A novel prognostic cancer-related lncRNA signature in papillary renal cell carcinoma. Cancer Cell Int 2021; 21:545. [PMID: 34663322 PMCID: PMC8525017 DOI: 10.1186/s12935-021-02247-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 10/05/2021] [Indexed: 01/20/2023] Open
Abstract
Background Papillary renal cell carcinoma (pRCC) ranks second in renal cell carcinoma and the prognosis of pRCC remains poor. Here, we aimed to screen and identify a novel prognostic cancer-related lncRNA signature in pRCC. Methods The RNA-seq profile and clinical feature of pRCC cases were downloaded from TCGA database. Significant cancer-related lncRNAs were obtained from the Immlnc database. Differentially expressed cancer-related lncRNAs (DECRLs) in pRCC were screened for further analysis. Cox regression report was implemented to identify prognostic cancer-related lncRNAs and establish a prognostic risk model, and ROC curve analysis was used to evaluate its precision. The correlation between RP11-63A11.1 and clinical characteristics was further analyzed. Finally, the expression level and role of RP11-63A11.1 were studied in vitro. Results A total of 367 DECRLs were finally screened and 26 prognostic cancer-related lncRNAs were identified. Among them, ten lncRNAs (RP11-573D15.8, LINC01317, RNF144A-AS1, TFAP2A-AS1, LINC00702, GAS6-AS1, RP11-400K9.4, LUCAT1, RP11-63A11.1, and RP11-156L14.1) were independently associated with prognosis of pRCC. These ten lncRNAs were incorporated into a prognostic risk model. In accordance with the median value of the riskscore, pRCC cases were separated into high and low risk groups. Survival analysis indicated that there was a significant difference on overall survival (OS) rate between the two groups. The area under curve (AUC) in different years indicated that the model was of high efficiency in prognosis prediction. RP11-63A11.1 was mainly expressed in renal tissues and it correlated with the tumor stage, T, M, N classifications, OS, PFS, and DSS of pRCC patients. Consistent with the expression in pRCC tissue samples, RP11-63A11.1 was also down-regulated in pRCC cells. More importantly, up-regulation of RP11-63A11.1 attenuated cell survival and induced apoptosis. Conclusions Ten cancer-related lncRNAs were incorporated into a powerful model for prognosis evaluation. RP11-63A11.1 functioned as a cancer suppressor in pRCC and it might be a potential therapeutic target for treating pRCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02247-6.
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Liu Y, Wu Q, Fan X, Li W, Li X, Zhu H, Zhou Q, Yu J. A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma. Sci Rep 2021; 11:16794. [PMID: 34408216 PMCID: PMC8373953 DOI: 10.1038/s41598-021-96236-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/06/2021] [Indexed: 02/05/2023] Open
Abstract
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.
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Affiliation(s)
- Yang Liu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Qiuhong Wu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xuejiao Fan
- Clinical Research Management Department, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Wen Li
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaogang Li
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
| | - Qinghua Zhou
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
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Qi B, Liu H, Zhou Q, Ji L, Shi X, Wei Y, Gu Y, Mizushima A, Xia S. An immune-related lncRNA signature for the prognosis of pancreatic adenocarcinoma. Aging (Albany NY) 2021; 13:18806-18826. [PMID: 34285140 PMCID: PMC8351726 DOI: 10.18632/aging.203323] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 07/08/2021] [Indexed: 12/12/2022]
Abstract
Recent evidence suggests that aberrant expression of long non-coding RNA (lncRNA) can drive the initiation and progression of malignancies. However, little is known about the prognostic potential of lncRNA. We aimed at constructing a lncRNA-based signature to improve the prognosis prediction of pancreatic adenocarcinoma (PAAD). The PAAD samples with clinical information were obtained from The Cancer Genome Atlas and International Cancer Genome Consortium. We established an eight-IRlncRNA signature in a training cohort. The prognostic value of eight-IRlncRNA signature was validated in two distinct cohorts when compared to other four prognostic models. We continued to analyze its independence in subgroups by univariate and multivariate Cox regression. We constructed a nomogram for clinicopathologic features and 1-, 3-, and 5-year overall survival performance. Moreover, Gene set enrichment analysis and Gene Set Variation Analysis distinguished the typical functions between high- and low-risk groups. In addition, we further observed the different correlations of immune cell between eight IRlncRNAs. Eight-IRlncRNA signature appears to be a good performer to predict the survival capability of PAAD patients, and the nomogram will enable PAAD patients to be more accurately managed in clinical practice.
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Affiliation(s)
- Bing Qi
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
| | - Han Liu
- College of Stomatology, Dalian Medical University, Dalian 116044, Liaoning, China
| | - Qi Zhou
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning, China
| | - Li Ji
- Department of Gastroenterology, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning, China
| | - Xueying Shi
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning, China
| | - Yushan Wei
- Department of Scientific Research, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
| | - Yajun Gu
- School of Medical Laboratory, Tianjin Medical University, Tianjin 300000, Tianjin, China
| | - Akio Mizushima
- Department of Palliative Medicine, Graduate School of Medicine, Juntendo University, Tokyo 1138421, Japan
| | - Shilin Xia
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
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Yin J, Li X, Lv C, He X, Luo X, Li S, Hu W. Immune-Related lncRNA Signature for Predicting the Immune Landscape of Head and Neck Squamous Cell Carcinoma. Front Mol Biosci 2021; 8:689224. [PMID: 34327215 PMCID: PMC8313825 DOI: 10.3389/fmolb.2021.689224] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 06/21/2021] [Indexed: 01/05/2023] Open
Abstract
Background: Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients. Methods: We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules. Results: A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan-Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor via the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups. Conclusion: The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.
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Affiliation(s)
- Ji Yin
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Xiaohui Li
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Caifeng Lv
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Xian He
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Xiaoqin Luo
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Sen Li
- Spinal Surgery Department, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Wenjian Hu
- Department of Otorhinolaryngology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
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Zhao F, Wang M, Zhu J. Hypoxia-related lncRNAs to build prognostic classifier and reveal the immune characteristics of EGFR wild type and low expression of PD-L1 squamous and adenocarcinoma NSCLC. Cancer Med 2021; 10:6099-6113. [PMID: 34250747 PMCID: PMC8419766 DOI: 10.1002/cam4.4126] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/16/2021] [Accepted: 06/25/2021] [Indexed: 02/05/2023] Open
Abstract
Background Recently, the development and application of targeted therapies like tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have achieved remarkable survival benefits in non‐small cell lung cancer (NSCLC) treatment. However, epidermal growth factor receptor (EGFR) wild type and low expression of programmed death‐ligand 1 (PD‐L1) NSCLC remain unmanageable. Few treatments for these patients exist, and more side effects with combination therapies have been observed. We intended to generate a hypoxia‐related lncRNAs (hypolncRNAs) classifier that could successfully identify the high‐risk patients and reveal its underlying molecular immunology characteristics. Methods By identifying the bottom 25% PD‐L1 expression level as low expression of PD‐L1 and removing EGFR mutant samples, a total of 222 lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) samples and 93 adjacent non‐tumor samples were finally extracted from The Cancer Genome Atlas (TCGA). A 0 or 1 matrix was constructed by cyclically pairing hypoxia‐related long non‐coding RNAs (hypolncRNAs) and divided into the train set and test set. The univariate Cox regression analysis determined the prognostic hypolncRNAs pairs. Then, the prognostic classifier contained nine hypolncRNAs pairs which were generated by Lasso regression and multivariate Cox analysis. It successfully stratified EGFR wild type and low expression of PD‐L1 squamous and adenocarcinoma NSCLC (double‐negative LUAD and LUSC) patients into the high‐ and low‐risk groups, whose accuracy was proved by the time‐dependent receiver operating characteristic (ROC) curve. Furthermore, diverse acknowledged immunology methods include XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT‐ABS, CIBERSORT, and the single‐sample gene set enrichment analysis (ssGSEA) revealed its underlying antitumor immunosuppressive status in the high‐risk patients. Conclusions It is noteworthy that hypolncRNAs are associated with the survival of double‐negative LUAD and LUSC patients, for which the possible mechanism is inhibiting the antitumor immune process.
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Affiliation(s)
- Fang Zhao
- Department of Intensive Care Unit, The Peoples Hospital of Tongliang District, Chongqing, China
| | - Min Wang
- Department of Respiratory and Geriatrics, Chongqing Public Health Medical Center, Chongqing, China
| | - Jie Zhu
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
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Yuan Q, Ren J, Li L, Li S, Xiang K, Shang D. Development and validation of a novel N6-methyladenosine (m6A)-related multi- long non-coding RNA (lncRNA) prognostic signature in pancreatic adenocarcinoma. Bioengineered 2021; 12:2432-2448. [PMID: 34233576 PMCID: PMC8806915 DOI: 10.1080/21655979.2021.1933868] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Accumulating evidence has unveiled the pivotal roles of N6-methyladenosine (m6A) in pancreatic adenocarcinoma (PAAD). However, there are not many researches to predict the prognosis of PAAD using m6A-related long non-coding RNAs (lncRNAs). Raw data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and the Genotype-Tissue Expression project (GTEx) were utilized to comprehensively analyze the expression and prognostic performances of 145 m6A-related lncRNAs in PAAD and to develop and validate a novel m6A-related multi-lncRNA prognostic signature (m6A-LPS) for PAAD patients. In total, 57 differentially expressed m6A-related lncRNAs with prognostic values were identified. Based on LASSO-Cox regression analysis, m6A-LPS was constructed and verified by using five-lncRNA expression profiles for TCGA and ICGC cohorts. PAAD patients were then divided into high- and low-risKBIE_A_1933868k subgroups with different clinical outcomes according to the median risk score; this was further verified by time-dependent receiver operating characteristic curves. Risk scores were significantly associated with clinical parameters such as histological grade and cancer status among PAAD patients. A nomogram consisting of risk score, grade, and cancer status was generated to predict the survival probability of PAAD patients, as also demonstrated by calibration curves. Discrepancies in cellular processes, signaling pathways, and immune status between the high- and low-risk subgroups were investigated by functional and single-sample gene set enrichment analyses. In conclusion, the novel m6A-LPS for PAAD patients was developed and validated, which might provide new insight into clinical decision-making and precision medicine.
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Affiliation(s)
- Qihang Yuan
- Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jie Ren
- Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Lunxu Li
- Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shuang Li
- Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Kailai Xiang
- Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dong Shang
- Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.,Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
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48
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Hong WF, Gu YJ, Wang N, Xia J, Zhou HY, Zhan K, Cheng MX, Cai Y. Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma. J Clin Transl Hepatol 2021; 9:301-314. [PMID: 34221916 PMCID: PMC8237144 DOI: 10.14218/jcth.2020.00132] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/18/2021] [Accepted: 02/21/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND AND AIMS Tumor microenvironment plays an essential role in cancer development and progression. Cancer immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma (HCC). We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic changes. METHODS Key immune-relevant genes (KIRGs) were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas, immune genes from the Immunology Database and Analysis Portal, and immune differentially expressed genes determined by single-sample gene set enrichment analysis scores. Cox regression analysis was performed to mine therapeutic target genes. A regulatory network based on KIRGs, transcription factors, and immune-related long non-coding RNAs (IRLncRNAs) was also generated. The outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry staining. Correlation analysis between risk score and immune checkpoint genes and immune cell infiltration were investigated. RESULTS In total, we identified 21 KIRGs, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), and found IKBKE, IL2RG, EDNRA, and IGHA1 may be equally important to PD-1 or CTLA4. Meanwhile, KIRGs, various transcription factors, and IRLncRNAs were integrated to reveal that the NRF1-AC127024.5-IKBKE axis might be involved in tumor immunity regulation. Furthermore, the immune-related risk score model was established according to KIRGs and key IRLncRNAs, and verified more obvious discriminating power in the testing cohort. Correlation analysis indicated TNFSF4 , LGALS9 , KIAA1429 , IDO2, and CD276 were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types. CONCLUSIONS Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.
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Affiliation(s)
- Wei-Feng Hong
- Department of Medical Imaging, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Yu-Jun Gu
- Department of Ultrasonic Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Na Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie Xia
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Heng-Yu Zhou
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- College of Nursing, Chongqing Medical University, Chongqing, China
| | - Ke Zhan
- Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ming-Xiang Cheng
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ying Cai
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Intensive Care Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Correspondence to: Ying Cai, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases; Department of Intensive Care Medicine, The Second Affiliated Hospital, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400000, China. ORCID: https://orcid.org/0000-0002-1782-719X. Tel: +86-15923330181, E-mail:
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Song W, He X, Gong P, Yang Y, Huang S, Zeng Y, Wei L, Zhang J. Glycolysis-Related Gene Expression Profiling Screen for Prognostic Risk Signature of Pancreatic Ductal Adenocarcinoma. Front Genet 2021; 12:639246. [PMID: 34249078 PMCID: PMC8261051 DOI: 10.3389/fgene.2021.639246] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/25/2021] [Indexed: 12/21/2022] Open
Abstract
Objective: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Although progress has been made in the treatment of PDAC, its prognosis remains unsatisfactory. This study aimed to develop novel prognostic genes related to glycolysis in PDAC and to apply these genes to new risk stratification. Methods: In this study, based on the Cancer Genome Atlas (TCGA) PAAD cohort, the expression level of glycolysis-related gene at mRNA level in PAAD and its relationship with prognosis were analyzed. Non-negative matrix decomposition (NMF) clustering was used to cluster PDAC patients according to glycolytic genes. Prognostic glycolytic genes, screened by univariate Cox analysis and LASSO regression analysis were established to calculate risk scores. The differentially expressed genes (DEGs) in the high-risk group and the low-risk group were analyzed, and the signal pathway was further enriched to analyze the correlation between glycolysis genes. In addition, based on RNA-seq data, CIBERSORT was used to evaluate the infiltration degree of immune cells in PDAC samples, and ESTIMATE was used to calculate the immune score of the samples. Results: A total of 319 glycolysis-related genes were retrieved, and all PDAC samples were divided into two clusters by NMF cluster analysis. Survival analysis showed that PDAC patients in cluster 1 had shorter survival time and worse prognosis compared with cluster 2 samples (P < 0.001). A risk prediction model based on 11 glycolysis genes was constructed, according to which patients were divided into two groups, with significantly poorer prognosis in high-risk group than in low-risk group (P < 0.001). Both internal validation and external dataset validation demonstrate good predictive ability of the model (AUC = 0.805, P < 0.001; AUC = 0.763, P < 0.001). Gene aggregation analysis showed that DEGs highly expressed in high-risk group were mainly concentrated in the glycolysis level, immune status, and tumor cell proliferation, etc. In addition, the samples in high-risk group showed immunosuppressed status and infiltrated by relatively more macrophages and less CD8+T cell. Conclusions: These findings suggested that the gene signature based on glycolysis-related genes had potential diagnostic, therapeutic, and prognostic value for PDAC.
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Affiliation(s)
- Wenjing Song
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Xin He
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Pengju Gong
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yan Yang
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Sirui Huang
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yifan Zeng
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Lei Wei
- Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Jingwei Zhang
- Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China
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50
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Lu L, Liu LP, Zhao QQ, Gui R, Zhao QY. Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma. Front Oncol 2021; 11:675545. [PMID: 34249715 PMCID: PMC8260838 DOI: 10.3389/fonc.2021.675545] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/08/2021] [Indexed: 12/16/2022] Open
Abstract
Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.
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Affiliation(s)
- Lu Lu
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Le-Ping Liu
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qiang-Qiang Zhao
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Rong Gui
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qin-Yu Zhao
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, China
- College of Engineering and Computer Science, Australian National University, Canberra, ACT, Australia
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