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Huang G, Chen S, He J, Li H, Ma Z, Lubamba GP, Wang L, Guo Z, Li C. Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance. Oral Dis 2025; 31:1116-1132. [PMID: 39503345 DOI: 10.1111/odi.15179] [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: 04/22/2024] [Revised: 09/14/2024] [Accepted: 10/16/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVE Histone lysine lactylation (Kla) plays a vital role in cancer progression. However, the prognostic value of histone Kla in oral squamous cell carcinoma (OSCC) remains unclear. MATERIALS AND METHODS OSCC RNA expression data were obtained from the TCGA and GEO databases. We explored the prognostic value of histone Kla in OSCC via constructing a Cox model and determined the role of Kla in OSCC drug susceptibility and tumor microenvironment (TME). In addition, the biological roles of candidate biomarkers were identified. RESULTS A total of 1223 Kla-specific genes were obtained, with 228 DEKlaGs in OSCC. GO and KEGG enrichment analyses suggested that DEKlaGs contributed to inflammatory and cancer progression. A Cox model in accordance with BCAM, CGNL1, DGKG, and OLR1 could predict OSCC patient prognosis accurately. Subsequently, Kla-induced prognostic genes were identified to play a crucial role in OSCC drug therapy and TME. Moreover, BCAM was identified as a biomarker that promoted OSCC invasion, angiogenesis, and chemotherapy resistance. CONCLUSION Kla was identified to be associated with OSCC prognosis, drug therapy, and TME. Histone Kla-induced BCAM was identified to play a crucial role during OSCC progression, suggesting that Kla is promising to be a novel therapeutic target for OSCC.
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Affiliation(s)
- Guangzhao Huang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Su Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jialu He
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Honglin Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhongkai Ma
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Grace Paka Lubamba
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lei Wang
- Department of Dentistry, The Second people's Hospital of Tibet Autonomous Region, Xizang, China
| | - Zhiyong Guo
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chunjie Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Frontier Innovation Center for Dental Medicine Plus, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Vargas-Rondón N, González-Giraldo Y, García Fonseca ÁY, Gonzalez J, Aristizabal-Pachon AF. MicroRNAs signatures as potential molecular markers in mild cognitive impairment: a meta-analysis. Front Aging Neurosci 2025; 16:1524622. [PMID: 39881680 PMCID: PMC11774935 DOI: 10.3389/fnagi.2024.1524622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 12/31/2024] [Indexed: 01/31/2025] Open
Abstract
Mild cognitive impairment (MCI) is characterized by a decline in cognitive functioning without significant interference in daily activities. Its high heterogeneity and elevated conversion rate to dementia pose challenges for accurate diagnosis and monitoring, highlighting the urgent need to identify methodologies focused on the early detection and intervention of MCI. Due to their biological characteristics, microRNAs (miRNAs) are potential candidates as non-invasive molecular markers for the identification and assessment of MCI progression. Therefore, in this study, we conducted a meta-analysis to identify the miRNAs commonly deregulated in MCI, focusing on expression profiles in plasma, serum, and extracellular vesicle samples. Our analysis identified eight upregulated miRNAs, including hsa-miR-149-3p, and four downregulated miRNAs, such as Let-7f-5p. Notably, hsa-miR-149-3p emerged as a central node in interaction networks, suggesting its crucial role in regulating cellular processes relevant to MCI. Additionally, pathway analysis revealed significant enrichment in biological processes associated with transcriptional regulation and neurodegeneration. Our results underscore the potential of circulating miRNAs as non-invasive molecular markers for MCI and open the possibility for new methodologies that enable more accurate diagnosis and monitoring of disease progression. Validating the expression of miRNAs such as hsa-miR-149-3p and Let-7f-5p, along with identifying their functional role in the specific context of MCI, is essential to establish their biological relevance. This work contributes to the understanding of the miRNA profile in mild cognitive impairment using easily accessible samples, which could be useful for the development of various strategies aimed at preventing or delaying MCI in individuals at risk of developing dementia, including Alzheimer's disease.
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Affiliation(s)
| | | | | | | | - Andrés Felipe Aristizabal-Pachon
- Experimental and Computational Biochemistry, Department of Nutrition and Biochemistry, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia
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Miao L, Chen B, Jing L, Zeng T, Chen Y. TPD52 as a Potential Prognostic Biomarker and its Correlation with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma: Bioinformatic Analysis and Experimental Verification. Recent Pat Anticancer Drug Discov 2025; 20:71-88. [PMID: 38305309 DOI: 10.2174/0115748928267447231107101539] [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: 06/15/2023] [Revised: 09/15/2023] [Accepted: 10/04/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND Aberrant expression of tumor protein D52 (TPD52) is associated with some tumors. The role of TPD52 in uterine corpus endometrial carcinoma (UCEC) remains uncertain. OBJECTIVE We aimed to investigate the involvement of TPD52 in the pathogenesis of UCEC. METHODS We employed bioinformatics analysis and experimental validation in our study. RESULTS Our findings indicated that elevated TPD52 expression in UCEC was significantly associated with various clinical factors, including clinical stage, race, weight, body mass index (BMI), histological type, histological grade, surgical approach, and age (p < 0.01). Furthermore, high TPD52 expression was a predictor of poorer overall survival (OS), progress-free survival (PFS), and disease-specific survival (DSS) (p = 0.011, p = 0.006, and p = 0.003, respectively). TPD52 exhibited a significant correlation with DSS (HR: 2.500; 95% CI: 1.153-5.419; p = 0.02). TPD52 was involved in GPCR ligand binding and formation of the cornified envelope in UCEC. Moreover, TPD52 expression was found to be associated with immune infiltration, immune checkpoints, tumor mutation burden (TMB)/ microsatellite instability (MSI), and mRNA stemness indices (mRNAsi). The somatic mutation rate of TPD52 in UCEC was 1.9%. A ceRNA network of AC011447.7/miR-1-3p/TPD52 was constructed. There was excessive TPD52 protein expression. The upregulation of TPD52 expression in UCEC cell lines was found to be statistically significant. CONCLUSION TPD52 is upregulated in UCEC and may be a useful patent for prognostic biomarkers of UCEC, which may have important value for clinical treatment and supervision of UCEC patients.
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Affiliation(s)
- Lu Miao
- Department of Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, 215026, Suzhou, Jiangsu, China
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221009, Jiangsu, China
| | - Buze Chen
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221009, Jiangsu, China
| | - Li Jing
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221009, Jiangsu, China
| | - Tian Zeng
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221009, Jiangsu, China
| | - Youguo Chen
- Department of Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, 215026, Suzhou, Jiangsu, China
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Wang D, Zhao XR, Li YF, Wang RL, Li XB, Wang CX, Li YW. Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR-149-3p/AKT1 axis. Kaohsiung J Med Sci 2024; 40:903-915. [PMID: 39162596 DOI: 10.1002/kjm2.12887] [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: 03/31/2024] [Revised: 07/25/2024] [Accepted: 07/28/2024] [Indexed: 08/21/2024] Open
Abstract
Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.
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Affiliation(s)
- Dan Wang
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Xin-Rui Zhao
- Chinese Medicine College, Hong Kong Baptist University, Kowloon City, Hong Kong, China
| | - Yi-Fan Li
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Rui-Lin Wang
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Xue-Bing Li
- Department of Clinical Laboratory Centre, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Chun-Xia Wang
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
- Department of Clinical Laboratory Centre, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
| | - Yong-Wei Li
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
- Department of Clinical Laboratory Centre, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China
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Cui M, Liu Y, Liu Y, Li T, Chen X, Da L. Oral nano-formulations for endocrine therapy of endometrioid adenocarcinomas. Biomed Pharmacother 2024; 179:117328. [PMID: 39243435 DOI: 10.1016/j.biopha.2024.117328] [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: 05/27/2024] [Revised: 08/04/2024] [Accepted: 08/21/2024] [Indexed: 09/09/2024] Open
Abstract
Endometrial cancer is one of the three major malignant tumors of the reproductive system that threaten women's lives and health. The incidence of this disease is on the rise globally. Most cases of endometrial cancer comprise endometrioid adenocarcinomas, whose treatment is challenged by factors such as their high recurrence rate and the need to preserve fertility among young patients. Thus, oral endocrine therapy has become the main treatment modality. The main drugs used in oral endocrine therapy are progestins, selective estrogen receptor antagonists, and aromatase inhibitors. However, their clinical use is hindered by their low solubility and low oral utilization. The rapid development of nanotechnology allows the combination of these drugs with oral nano-formulations to create a good carrier. Such nanocarriers, including nanospheres, nanocapsules, and micelles can protect the drug against clearance and increase the site specificity of drug delivery. This paper reviews the pathogenesis of endometrioid endometrial cancer (EEC) and oral nano-formulations for endocrine therapy.
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Affiliation(s)
- Minghua Cui
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; Gynecology Department, Affliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China.
| | - Yuehui Liu
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; Laboratory Department, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China.
| | - Yangyang Liu
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; Laboratory Department, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China.
| | - Tao Li
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; Department of Acupuncture and Massage, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China.
| | - Xin Chen
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; Gynecology Department, Affliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, China.
| | - Liu Da
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
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Mu H, Ye L, Wang B. Detailed resume of S-methyltransferases: Categories, structures, biological functions and research advancements in related pathophysiology and pharmacotherapy. Biochem Pharmacol 2024; 226:116361. [PMID: 38876259 DOI: 10.1016/j.bcp.2024.116361] [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: 03/05/2024] [Revised: 05/19/2024] [Accepted: 06/10/2024] [Indexed: 06/16/2024]
Abstract
Methylation is a vital chemical reaction in the metabolism of many drugs, neurotransmitters, hormones, and exogenous compounds. Among them, S-methylation plays a significant role in the biotransformation of sulfur-containing compounds, particularly chemicals with sulfhydryl groups. Currently, only three S-methyltransferases have been reported: thiopurine methyltransferase (TPMT), thiol methyltransferase (TMT), and thioether methyltransferase (TEMT). These enzymes are involved in various biological processes such as gene regulation, signal transduction, protein repair, tumor progression, and biosynthesis and degradation reactions in animals, plants, and microorganisms. Furthermore, they play pivotal roles in the metabolic pathways of essential drugs and contribute to the advancement of diseases such as tumors. This paper reviews the research progress on relevant structural features, metabolic mechanisms, inhibitor development, and influencing factors (gene polymorphism, S-adenosylmethionine level, race, sex, age, and disease) of S-methyltransferases. We hope that a better comprehension of S-methyltransferases will help to provide a reference for the development of novel strategies for related disorders and improve long-term efficacy.
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Affiliation(s)
- Hongfei Mu
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
| | - Lisha Ye
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
| | - Baolian Wang
- Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
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Zhao L, Zheng H, Chen F, Lu H, Yu Q, Yan X, Chen X, Zhang Q, Bu Q. High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma. Curr Mol Med 2024; 24:801-812. [PMID: 37340746 DOI: 10.2174/1566524023666230619123752] [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: 01/04/2023] [Revised: 05/16/2023] [Accepted: 05/17/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD. OBJECTIVE In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation. METHODS We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. RESULT In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18-2.1; P=0.002). And TLX1 HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells. CONCLUSION An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.
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Affiliation(s)
- Liang Zhao
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Haiping Zheng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Feng Chen
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Huasong Lu
- Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Qian Yu
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Xuexin Yan
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Xinyu Chen
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Qianyu Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Qing Bu
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
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Ding X, Wan A, Qi X, Jiang K, Liu Z, Chen B. ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification. Curr Gene Ther 2024; 24:441-452. [PMID: 38441026 DOI: 10.2174/0115665232285216240228071244] [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: 10/02/2023] [Revised: 01/01/1970] [Accepted: 02/19/2024] [Indexed: 03/06/2024]
Abstract
BACKGROUND The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). OBJECTIVE The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC. METHODS The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570. RESULTS ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines. CONCLUSION ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.
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Affiliation(s)
- Xiaojuan Ding
- Graduate School, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
- The Fifth People's Hospital of Huai'an, Huai'an 223300, Jiangsu, China
| | - Ailing Wan
- Graduate School, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
- The Fifth People's Hospital of Huai'an, Huai'an 223300, Jiangsu, China
| | - Xin Qi
- Graduate School, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
- The Fifth People's Hospital of Huai'an, Huai'an 223300, Jiangsu, China
| | - Ke'er Jiang
- Graduate School, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Zhao Liu
- The First Clinical Medical College, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Buze Chen
- The First Clinical Medical College, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
- Huaihai Institute of Traditional Chinese Medicine, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
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Liang D, Zhang Q, Pang Y, Yan R, Ke Y. SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity. Protein Pept Lett 2024; 31:894-905. [PMID: 39501960 DOI: 10.2174/0109298665341953240926041613] [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: 07/24/2024] [Revised: 09/10/2024] [Accepted: 09/10/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND The abnormal expression of small G protein signaling modulator 2 (SGSM2) is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2 in uveal melanoma (UVM) is unclear. OBJECTS To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental validation. METHODS The expression of SGSM2 was detected in UVM cell lines through quantitative real-- time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship between SGSM2 expression and clinical characteristics, as well as its prognostic significance in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2 in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing data. RESULTS SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2 in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress- free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally, SGSM2 expression was identified as an independent prognostic factor in UVM patients (p < 0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway, natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in UVM patients. CONCLUSION SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients.
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Affiliation(s)
- Demao Liang
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China
| | - Qiuli Zhang
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China
| | - Yanhua Pang
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China
| | - Rili Yan
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China
| | - Yi Ke
- Department of Ophthalmology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong, China
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Cai H, Chen S, Wu Z, Wang F, Tang S, Li D, Wang D, Guo W. Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma. Aging (Albany NY) 2023; 15:13041-13058. [PMID: 37980166 DOI: 10.18632/aging.205218] [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: 05/30/2023] [Accepted: 10/02/2023] [Indexed: 11/20/2023]
Abstract
Currently, the roles of ZNF692 have been documented exclusively in lung, colon, and cervical cancers. However, its involvement in pan cancer remains unknown. In this study, we employed bioinformatics analysis and experimental validation to investigate the role of ZNF692 in pan cancer. Our findings revealed aberrant expression of ZNF692 across various types of cancer. High expression of ZNF692 was associated with poor overall survival (OS) in ACC, COAD, KIRC, LAML, and LIHC. ZNF692 exhibited promising diagnostic potential in certain tumor types. A significant correlation was observed between high ZNF692 expression and advanced stages of ACC, BLCA, KICH, KIRC, LIHC, and OV. The expression of ZNF692 exhibited a significant association with microsatellite instability (MSI) in eight types of cancer and tumor mutational burden (TMB) in ten types of cancer. A noteworthy correlation was observed between ZNF692 expression and immune infiltration as well as immune checkpoints. Amplification of ZNF692 emerged as the most frequent alteration in pan cancer. ZNF692 was implicated in various biological processes, cellular components, and molecular functions within the context of pan cancer. It is plausible that ZNF692 may contribute to chemotherapy and potentially be linked to chemoresistance. We constructed a competing endogenous RNA (ceRNA) network involving AC009403.11/miR-126-3p/ZNF692 in hepatocellular carcinoma (HCC). The expression of ZNF692 exhibited a notable upregulation in HCC cell lines. Aberrant expression of ZNF692 was observed across various types of cancer. ZNF692 holds potential as a valuable diagnostic, prognostic, and therapeutic target in the context of pan cancer.
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Affiliation(s)
- Hongjie Cai
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510062, Guangdong, China
| | - Song Chen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center and Sun Yat-Sen University State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong, China
| | - Zhiqiang Wu
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510062, Guangdong, China
| | - Fan Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510062, Guangdong, China
| | - Shuangyan Tang
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510062, Guangdong, China
| | - Dongbing Li
- Department of Translational Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Dongliang Wang
- Department of Translational Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Wenbo Guo
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510062, Guangdong, China
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Liu X, Zeng L, Wang W, Li Z, Zhou S, Wang F, Wang Y, Du J, Ma X. Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC. Oncol Lett 2023; 26:435. [PMID: 37664656 PMCID: PMC10472046 DOI: 10.3892/ol.2023.14022] [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: 04/01/2023] [Accepted: 07/14/2023] [Indexed: 09/05/2023] Open
Abstract
Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC. RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.
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Affiliation(s)
- Xiaoyan Liu
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
| | - Lili Zeng
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Wenlong Wang
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Zhipeng Li
- Department of Stomatology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang 314001, P.R. China
| | - Siyuan Zhou
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
- School of Stomatology, Binzhou Medical University, Yantai, Shandong 264000, P.R. China
| | - Fang Wang
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Yue Wang
- Department of Stomatology, Zibo Central Hospital, Zibo, Shandong 255000, P.R. China
| | - Jing Du
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
| | - Xiangrui Ma
- Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256600, P.R. China
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Chen B, Ding X, Wan A, Qi X, Lin X, Wang H, Mu W, Wang G, Zheng J. Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer. Sci Rep 2023; 13:16244. [PMID: 37758722 PMCID: PMC10533500 DOI: 10.1038/s41598-023-42171-5] [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: 06/07/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
T cell leukemia homeobox 2 (TLX2) plays an important role in some tumors. Bioinformatics and experimental validation represent a useful way to explore the mechanisms and functions of TLX2 gene in the cancer disease process from a pan cancer perspective. TLX2 was aberrantly expressed in pan cancer and cell lines and correlated with clinical stage. High TLX2 expression was significantly associated with poor overall survival in COAD, KIRC, OC, and UCS. The greatest frequency of TLX2 alterations in pan cancer was amplification. Alterations of NXF2B, MSLNL, PCGF1, INO80B-WBP1, LBX2-AS1, MRPL53, LBX2, TTC31, WDR54, and WBP1 co-occurred in the TLX2 alteration group. PFS was significantly shorter in the TLX2-altered group (n = 6) compared to the TLX2-unaltered group (n = 400). Methylation levels of TLX2 were high in 17 tumors. TLX2 expression was associated with MSI in seven tumors and TMB in five tumors. TLX2 expression was associated with immune infiltration and immune checkpoint genes. TLX2 may be associated with some pathways and chemoresistance. We constructed a possible competing endogenous RNA (ceRNA) network of LINC01010/miR-146a-5p/TLX2 in OC. TLX2 expression was significantly upregulated in ovarian cancer cell lines compared to ovarian epithelial cell lines. Aberrant expression of TLX2 in pan cancer may promote tumorigenesis and progression through different mechanisms. TLX2 may represent an important therapeutic target for human cancers.
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Affiliation(s)
- Buze Chen
- Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
- Cancer Institute, Xuzhou Medical University, No. 209 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, China.
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China.
| | - Xiaojuan Ding
- Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Ailing Wan
- Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Xin Qi
- Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Xiaoman Lin
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China
| | - Haihong Wang
- Department of Gynecology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China
| | - Wenyu Mu
- Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Gang Wang
- Cancer Institute, Xuzhou Medical University, No. 209 Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, China.
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China.
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
| | - Junnian Zheng
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China.
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
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Chen YC, Li DB, Wang DL, Peng H. Comprehensive analysis of distal-less homeobox family gene expression in colon cancer. World J Gastrointest Oncol 2023; 15:1019-1035. [PMID: 37389108 PMCID: PMC10302991 DOI: 10.4251/wjgo.v15.i6.1019] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/06/2023] [Accepted: 04/27/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND The distal-less homeobox (DLX) gene family plays an important role in the development of several tumors. However, the expression pattern, prognostic and diagnostic value, possible regulatory mechanisms, and the relationship between DLX family genes and immune infiltration in colon cancer have not been systematically reported.
AIM We aimed to comprehensively analyze the biological role of the DLX gene family in the pathogenesis of colon cancer.
METHODS Colon cancer tissue and normal colon tissue samples were collected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Wilcoxon rank sum test and t-test were used to assess DLX gene family expression between colon cancer tissue and unpaired normal colon tissue. cBioPortal was used to analyze DLX gene family variants. R software was used to analyze DLX gene expression in colon cancer and the relationship between DLX gene family expression and clinical features and correlation heat map. The survival package and Cox regression module were used to assess the prognostic value of the DLX gene family. The pROC package was used to analyze the diagnostic value of the DLX gene family. R software was used to analyze the possible regulatory mechanisms of DLX gene family members and related genes. The GSVA package was used to analyze the relationship between the DLX gene family and immune infiltration. The ggplot2, the survminer package, and the clusterProfiler package were used for visualization.
RESULTS DLX1/2/3/4/5 were significantly aberrantly expressed in colon cancer patients. The expression of DLX genes were associated with M stage, pathologic stage, primary therapy outcome, residual tumor, lymphatic invasion, T stage, N stage, age, perineural invasion, and history of colon polyps. DLX5 was independently correlated with the prognosis of colon cancer in multivariate analysis. DLX1/2/3/4/5/6 were involved in the development and progression of colon cancer by participating in immune infiltration and associated pathways, including the Hippo signaling pathway, the Wnt signaling pathway, several signaling pathways regulating the pluripotency of stem cells, and Staphylococcus aureus infection.
CONCLUSION The results of this study suggest a possible role for the DLX gene family as potential diagnostic or prognostic biomarkers and therapeutic targets in colon cancer.
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Affiliation(s)
- Yong-Cheng Chen
- Department of General Surgery (Endoscopic Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Dong-Bing Li
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Dong-Liang Wang
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Hui Peng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
- Department of General Surgery (Anorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
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Huang L, Yuan X, Zhao L, Han Q, Yan H, Yuan J, Guan S, Xu X, Dai G, Wang J, Shi Y. Gene signature developed for predicting early relapse and survival in early-stage pancreatic cancer. BJS Open 2023; 7:7169392. [PMID: 37196196 DOI: 10.1093/bjsopen/zrad031] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 01/23/2023] [Accepted: 02/23/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND The aim of this study was to construct a predictive signature integrating tumour-mutation- and copy-number-variation-associated features using machine learning to precisely predict early relapse and survival in patients with resected stage I-II pancreatic ductal adenocarcinoma. METHODS Patients with microscopically confirmed stage I-II pancreatic ductal adenocarcinoma undergoing R0 resection at the Chinese PLA General Hospital between March 2015 and December 2016 were enrolled. Whole exosome sequencing was performed, and genes with different mutation or copy number variation statuses between patients with and without relapse within 1 year were identified using bioinformatics analysis. A support vector machine was used to evaluate the importance of the differential gene features and to develop a signature. Signature validation was performed in an independent cohort. The associations of the support vector machine signature and single gene features with disease-free survival and overall survival were assessed. Biological functions of integrated genes were further analysed. RESULTS Overall, 30 and 40 patients were included in the training and validation cohorts, respectively. Some 11 genes with differential patterns were first identified; using a support vector machine, four features (mutations of DNAH9, TP53, and TUBGCP6, and copy number variation of TMEM132E) were further selected and integrated to construct a predictive signature (the support vector machine classifier). In the training cohort, the 1-year disease-free survival rates were 88 per cent (95 per cent c.i. 73 to 100) and 7 per cent (95 per cent c.i. 1 to 47) in the low-support vector machine subgroup and the high-support vector machine subgroup respectively (P < 0.001). Multivariable analyses showed that high support vector machine was significantly and independently associated with both worse overall survival (HR 29.20 (95 per cent c.i. 4.48 to 190.21); P < 0.001) and disease-free survival (HR 72.04 (95 per cent c.i. 6.74 to 769.96); P < 0.001). The area under the curve of the support vector machine signature for 1-year disease-free survival (0.900) was significantly larger than the area under the curve values of the mutations of DNAH9 (0.733; P = 0.039), TP53 (0.767; P = 0.024), and TUBGCP6 (0.733; P = 0.023), the copy number variation of TMEM132E (0.700; P = 0.014), TNM stage (0.567; P = 0.002), and differentiation grade (0.633; P = 0.005), suggesting higher predictive accuracy for prognosis. The value of the signature was further validated in the validation cohort. The four genes included in the support vector machine signature (DNAH9, TUBGCP6, and TMEM132E were novel in pancreatic ductal adenocarcinoma) were significantly associated with the tumour immune microenvironment, G protein-coupled receptor binding and signalling, cell-cell adhesion, etc. CONCLUSION The newly constructed support vector machine signature precisely and powerfully predicted relapse and survival in patients with stage I-II pancreatic ductal adenocarcinoma after R0 resection.
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Affiliation(s)
- Lei Huang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Medical Centre on Ageing of Ruijin Hospital, MCARJH, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiaodong Yuan
- Organ Transplant Center, Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Liangchao Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Quanli Han
- Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Huan Yan
- Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Jing Yuan
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
| | - Shasha Guan
- Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Xiaofeng Xu
- Shanghai Chief Technician Studio (Information & Technology), Shanghai, China
| | - Guanghai Dai
- Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China
| | - Junqing Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Shi
- Department of General Surgery, Shanghai Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Han QL, Cui Z, Wang Q, Pang F, Li D, Wang D. Upregulation of OTX2-AS1 is Associated With Immune Infiltration and Predicts Prognosis of Gastric Cancer. Technol Cancer Res Treat 2023; 22:15330338231154091. [PMID: 36740995 PMCID: PMC9905030 DOI: 10.1177/15330338231154091] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND It is unclear whether the long non-coding RNA (lncRNA) OTX2 antisense RNA 1 (OTX2-AS1) plays a pivotal role in gastric cancer (GC). An analysis of The Cancer Genome Atlas (TCGA) database data and bioinformatics was used to explore the relationship between OTX2-AS1 and GC in the current study. METHODS We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan-Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. GC cell lines were tested for OTX2-AS1 expression using qRT-PCR. RESULTS A high level of OTX2-AS1 expression was significantly and negatively associated with Helicobacter pylori (H pylori) infection in GC patients (P = .006) and predicted a poorer overall survival (OS) (HR: 1.54; 95% CI: 1.10-2.14; P = .011), progression-free interval (PFI) (HR: 1.75; 95% CI: 1.22-2.51; P = .002) and disease-specific survival (DSS) (HR: 1.85; 95% CI: 1.21-2.85; P = .005) in GC patients. There was an independent correlation between OTX2-AS1 expression (HR: 1.771; 95% CI: 1.164-2.696; P = .008) and OS in patients with GC. There were differential enrichments for the OTX2-AS1 high expression phenotype in the olfactory transduction, G alpha (s) signaling events, keratinization, olfactory signaling pathway, and preimplantation embryo. OTX2-AS1 expression may be related to certain immune-infiltrating cells. Compared to gastric epithelial cells (GES-1), GC cell lines showed a significant increase in OTX2-AS1 expression. CONCLUSION There was a significant association between OTX2-AS1 expression in GC patients and poor survival, suggesting that it may be a useful biomarker for prognosis and immunotherapy outcome of stomach adenocarcinoma (STAD) in GC.
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Affiliation(s)
- Quan-li Han
- Medical Oncology Department, The First Medical Center, Chinese PLA General Hospital, Beijing, China,Quan-li Han, Medical Oncology Department, The First Medical Center, Chinese PLA General Hospital, Beijing, China, 28 Fuxing Road, Haidian District, Beijing 100853, China.
| | - Zhi Cui
- Medical Oncology Department, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qi Wang
- Medical Oncology Department, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Fang Pang
- School of Medicine, Nankai University, Tianjin, China
| | - Dongbing Li
- ChosenMed Technology (Beijing) Co., Ltd, Beijing, China
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Huang H, Xu Q, Zhang Y, Zhou Y, Ma K, Luo Y. miR-628-5p is a Potential Novel Prognosis Biomarker, Associated with Immune Infiltration in Bladder Urothelial Carcinoma. Curr Pharm Des 2023; 29:2477-2488. [PMID: 37916623 DOI: 10.2174/0113816128254621231017062923] [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: 03/23/2023] [Revised: 08/23/2023] [Accepted: 09/08/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND microRNA-628-5p (miR-628-5p) has a significant impact on certain types of cancer. The precise function of miR-628-5p in the context of bladder urothelial carcinoma (BLCA) remains ambiguous. OBJECTIVE We aimed to investigate the role of miR-628-5p in BLCA. METHODS The samples were collected from The Cancer Genome Atlas (TCGA). Statistics were employed to evaluate the correlation and predictive significance of miR-628-5p. We analyzed the target genes and regulatory network of miR-628-5p and the correlation between miR-628-5p and immune infiltration. The expression of miR-628-5p in BLCA cells was confirmed by quantitative reverse-transcription PCR (qRT-PCR). RESULTS miR-628-5p exhibited differential expression across various types of cancer. There was a significant association between high expression of miR-628-5p and primary therapy outcome (p < 0.05). High expression of miR-628-5p was observed to be associated with poorer overall survival (HR: 1.42; 95% CI: 1.06-1.90; p = 0.02), progress free survival (HR: 1.57; 95% CI: 1.17-2.11; p = 0.003), and disease specific survival (HR: 1.83; 95% CI: 1.28-2.62; p = 0.001) in BLCA. miR-628-5p was an independent prognostic factor in BLCA and may be involved in the development of the disease through various pathways, including focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway, and among others. miR-628-5p expression was significantly correlated with immune infiltration in BLCA patients. Compared to normal bladder epithelial cells, BLCA cell lines exhibited a significant upregulation of miR-628-5p. CONCLUSION It is possible that miR-628-5p could serve as a hopeful therapeutic target and prognostic biomarker for individuals with BLCA.
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Affiliation(s)
- Hong Huang
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
| | - Qingchun Xu
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
| | - Yonghai Zhang
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
| | - Yizhou Zhou
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
| | - Kaiqun Ma
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
| | - Yingxun Luo
- Department of Urology, Shantou Central Hospital, Jinping District, Shantou 515031, China
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Yang D, Liu M, Jiang J, Luo Y, Wang Y, Chen H, Li D, Wang D, Yang Z, Chen H. Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma. Cancers (Basel) 2022; 14:cancers14246220. [PMID: 36551704 PMCID: PMC9777283 DOI: 10.3390/cancers14246220] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/12/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.
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Affiliation(s)
- Donghong Yang
- Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Meilian Liu
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Junhong Jiang
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Yiping Luo
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Yongcun Wang
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Huoguang Chen
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Dongbing Li
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Dongliang Wang
- Department of Medicine, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China
| | - Zhixiong Yang
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
- Correspondence: (Z.Y.); (H.C.); Tel.: +86-0759-2387458 (Z.Y.); +86-0759-2387458 (H.C.)
| | - Hualin Chen
- Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
- Correspondence: (Z.Y.); (H.C.); Tel.: +86-0759-2387458 (Z.Y.); +86-0759-2387458 (H.C.)
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Lin Z, Huang W, Xie Z, Yi Y, Li Z. Expression, Clinical Significance, Immune Infiltration, and Regulation Network of miR-3940-5p in Lung Adenocarcinoma Based on Bioinformatic Analysis and Experimental Validation. Int J Gen Med 2022; 15:6451-6464. [PMID: 35966511 PMCID: PMC9365057 DOI: 10.2147/ijgm.s375761] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 07/20/2022] [Indexed: 11/23/2022] Open
Abstract
Background Based on bioinformatics analysis and experimental validation, we investigated the expression, clinical significance, immune infiltration, and potential signaling pathways of miR-3940-5p in lung adenocarcinoma (LUAD). Methods 521 LUAD tissue samples and 46 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. We evaluated the relationship between clinical features and miR-3940-5p expression using Kruskal–Wallis, Wilcoxon sign-rank, and logistic regression, explored the relationship between miR-3940-5p expression and the prognosis of LUAD patients using Kaplan–Meier survival curve analysis. Several databases were used to identify miRNA targets. MiR-3940-5p target genes were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The significant role of miR-3940-5p in function was evaluated using immune infiltration analysis. LUAD cell lines were tested for miR-3940-5p expression using QRT-PCR. Results There was a significant association between high miR-3940-5p expression in LUAD and T stage (P=0.005), pathologic stage (P=0.047), race (White vs Asian & Black or African American) (P=0.041), residual tumor (P=0.043), and anatomic neoplasm subdivision2 (P=0.030). MiR-3940-5p expression predicted poor overall survival (HR: 1.35; 95% CI: 1.01–1.81; P=0.045), disease-specific survival (HR: 1.53; 95% CI: 1.05–2.23; P=0.026), and progression-free survival (HR: 1.35; 95% CI: 1.03–1.77; P=0.032). BAP1, BBS1, CCR2, KCNE3, PEBP1, and RABL2A were all associated with poor OS in LUAD patients with low miR-3940-5p expression levels. According to GO and KEGG analyses, miR-3940-5p may play a role in LUAD development by regulating pathways such as measles, PI3K-Akt signaling pathway, and p53 signaling pathway. There was a correlation between the expression level of miR-3940-5p and immune infiltration. LUAD cell lines showed significantly higher levels of miR-3940-5p than Beas-2B cells. Conclusion A high expression of miR-3940-5p is significantly associated with a poor prognosis in patients with LUAD, suggesting that it could be used as a prognostic biomarker.
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Affiliation(s)
- Zhichao Lin
- Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China
| | - Wenhai Huang
- Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China
| | - Zehua Xie
- Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China
| | - Yongsheng Yi
- Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China
| | - Zumei Li
- Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China
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