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Du Q, Meng C, Zhang W, Huang L, Xue C. Establishing a Prognostic Model Correlates to Inflammatory Response Pathways for Prostate Cancer via Multiomic Analysis of Lactylation-Related Genes. Int J Genomics 2025; 2025:6681711. [PMID: 40161494 PMCID: PMC11952923 DOI: 10.1155/ijog/6681711] [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: 12/14/2024] [Accepted: 02/25/2025] [Indexed: 04/02/2025] Open
Abstract
Prostate cancer (PCa) continues to pose substantial clinical challenges, with molecular heterogeneity significantly impacting therapeutic decision-making and disease trajectories. Emerging evidence implicates protein lactylation-a novel epigenetic regulatory mechanism-in oncogenic processes, though its prognostic relevance in PCa remains underexplored. Through integrative bioinformatics interrogation of lactylation-associated molecular signatures, we established prognostic correlations using multivariable feature selection methodologies. Initial screening via differential expression analysis (limma package) coupled with Cox proportional hazards modeling revealed 11 survival-favorable regulators and 16 hazard-associated elements significantly linked to biochemical recurrence. To enhance predictive precision, ensemble machine learning frameworks were implemented, culminating in a 10-gene lactylation signature demonstrating robust discriminative capacity (concordance index = 0.738) across both primary (TCGA-PRAD) and external validation cohorts (DKFZ). Multivariable regression confirmed the lactylation score's prognostic independence, exhibiting prominent associations with clinicopathological parameters including tumor staging and metastatic potential. The developed clinical-molecular nomogram achieved superior predictive accuracy (C - index > 0.7) through the synergistic integration of biological and clinical covariates. Tumor microenvironment deconvolution uncovered distinct immunological landscapes, with high-risk stratification correlating with enriched stromal infiltration and immunosuppressive phenotypes. Pathway enrichment analyses implicated chromatin remodeling processes and cytokine-mediated inflammatory cascades as potential mechanistic drivers of prognostic divergence. Therapeutic vulnerability profiling demonstrated differential response patterns: low-risk patients exhibited enhanced immune checkpoint inhibitor responsiveness, whereas high-risk subgroups showed selective chemosensitivity to docetaxel and mitoxantrone. Functional validation in PC-3 models revealed AK5 silencing induced proapoptotic effects, suppressed metastatic potential of migration and invasion, and modulated immune checkpoint regulation through CD276 coexpression. These multimodal findings position lactylation dynamics, particularly AK5-mediated pathways, as promising therapeutic targets and stratification biomarkers in PCa management.
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Affiliation(s)
- Qinglong Du
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - CuiYu Meng
- The Department of EICU, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, China
| | - Wenchao Zhang
- The Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, China
| | - Li Huang
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou, Guangdong, China
| | - Chunlei Xue
- The Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, China
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Yu Y, Lu XH, Mu JS, Meng JY, Sun JS, Chen HX, Yan Y, Meng K. N6-methyladenosine-modified long non-coding RNA KIF9-AS1 promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression. World J Gastroenterol 2024; 30:5174-5190. [PMID: 39735272 PMCID: PMC11612700 DOI: 10.3748/wjg.v30.i48.5174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 09/26/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC. Our previous study revealed that the long non-coding RNA (lncRNA) KIF9-AS1 is an oncogenic gene in HCC. However, the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear. Herein, we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC. AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism. METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients. Sphere formation was quantified via a tumor sphere assay. Cell viability, proliferation, and apoptosis were evaluated via Cell Counting Kit-8, flow cytometry, and colony formation assays, respectively. The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation. The tumorigenic role of KIF9-AS1 was validated in a mouse model. RESULTS Compared with that in normal controls, the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues. Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells. Mechanistically, N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1. Additionally, KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination. Furthermore, depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC. CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.
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MESH Headings
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/metabolism
- Sorafenib/pharmacology
- Sorafenib/therapeutic use
- Humans
- Liver Neoplasms/genetics
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/metabolism
- Drug Resistance, Neoplasm/genetics
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Animals
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- Mice
- Gene Expression Regulation, Neoplastic
- Up-Regulation
- Adenosine/analogs & derivatives
- Adenosine/metabolism
- Adenosine/pharmacology
- Cell Line, Tumor
- Male
- Cell Proliferation/drug effects
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Xenograft Model Antitumor Assays
- Apoptosis/drug effects
- Mice, Nude
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Methyltransferases/metabolism
- Methyltransferases/genetics
- Female
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Affiliation(s)
- Yong Yu
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Xiang-Hong Lu
- Department of Intensive Care Medicine, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Jin-Song Mu
- Department of Intensive Care Medicine, The Fifth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jiang-Yun Meng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Jiang-Shan Sun
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Hai-Xu Chen
- Institute of Geriatrics and National Clinical Research Center of Geriatrics Disease, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Yang Yan
- Department of General Surgery, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Ke Meng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
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Guo Y, Wu P, Liao Q, Huang Z. Association of DNA methylation of RASSF1A and SHOX2 with lung cancer risk: A systematic review and meta-analysis. Medicine (Baltimore) 2024; 103:e40042. [PMID: 39686414 PMCID: PMC11651524 DOI: 10.1097/md.0000000000040042] [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] [Received: 06/08/2024] [Accepted: 09/20/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND This study estimates the research upon the potential worth of Ras association domain family member 1 A (RASSF1A) and short stature homeobox 2 (SHOX2) DNA methylation in lung cancer (LC) diagnosis. METHODS Open-published research was searched through PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Chinese Biology Medicine Literature Database. Data on true positives, false positives, false negatives, and true negatives were extracted. RESULTS This meta-analysis included 22 studies encompassing 4109 subjects (2427 LC patients and 1682 controls). The combined sensitivity, specificity, and area under the curve for RASSF1A and SHOX2 DNA methylation were 0.77 (95% CI: 0.71-0.81), 0.90 (95% CI: 0.87-0.92), and 0.92 (95% CI: 0.87-0.92), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 7.5 (5.9-9.7) and 0.26 (0.21-0.32). The combined diagnostic odds ratio was 29 (95% CI: 20-41). CONCLUSION RASSF1A and SHOX2 DNA methylation may emerge as potential diagnostic biomarkers for early-stage LC.
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Affiliation(s)
- Yixin Guo
- Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Peiyi Wu
- Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Qiwei Liao
- Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
| | - Zhuo Huang
- Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, Guangdong, China
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Zhang H, Qian Y, Zhang Y, Zhou X, Shen S, Li J, Sun Z, Wang W. Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression. NPJ Precis Oncol 2024; 8:272. [PMID: 39572698 PMCID: PMC11582705 DOI: 10.1038/s41698-024-00764-x] [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: 06/29/2024] [Accepted: 11/11/2024] [Indexed: 11/24/2024] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck, associated with high recurrence and poor prognosis. We performed an integrated analysis of single-cell RNA and spatial transcriptomic data from cancerous and normal tissues to create a comprehensive atlas of epithelial cells and cancer-associated fibroblasts (CAFs). Our findings show that AKR1C3+ epithelial cells, located at the tumor's stromal front, exhibit significant copy number variation and poor prognostic indicators, suggesting a role in tumor invasion. We also identified a distinct group of early-stage CAFs (named OSCC_Normal, characterized by ADH1B+, MFAP4+, and PLA2G2A+) that interact with AKR1C3+ cells, where OSCC_Normal may inhibit the FOXO1 redox switch in these epithelial cells via the IGF1/IGF1R pathway, causing oxidative stress overload. Conversely, AKR1C3+ cells use ITGA6/ITGB4 receptor to counteract the effects of OSCC_Normal, promoting cancer invasion. This study unveils complex interactions within the OSCC tumor microenvironment.
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Affiliation(s)
- Hongrong Zhang
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
- Yunnan Key Laboratory of Stomatology, Kunming, China
| | - Yemei Qian
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
- Yunnan Key Laboratory of Stomatology, Kunming, China
| | - Yang Zhang
- Department of Vascular Surgery, Fuwai Yunnan Cardiovascular Hospital, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, China
| | - Xue Zhou
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
| | - Shiying Shen
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
- Yunnan Key Laboratory of Stomatology, Kunming, China
| | - Jingyi Li
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China
| | - Zheyi Sun
- Yunnan Key Laboratory of Stomatology, Kunming, China.
- Department of Endodontics, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China.
| | - Weihong Wang
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China.
- Yunnan Key Laboratory of Stomatology, Kunming, China.
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Chen X, Li S, Sun B. Downregulation of short-stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β-catenin signaling. Drug Dev Res 2024; 85:e70006. [PMID: 39415634 DOI: 10.1002/ddr.70006] [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: 06/08/2024] [Revised: 09/20/2024] [Accepted: 09/29/2024] [Indexed: 10/19/2024]
Abstract
Gastric cancer (GC) a prevalent form of cancer globally. Previous research suggests that SHOX2 may have a role in promoting cancer progression. However, the role of SHOX2 in GC is not well understood. Based on data from TCGA_GC data set, SHXO2 levels were examined in normal and GC tissues. Patients in the TCGA_GC cohort were divided into high- and low-SHOX2 level groups for analysis of overall survival (OS), functional enrichment, and immune infiltration. Furthermore, experiments were conducted to investigate the impact of SHOX2 on GC cell function through gain- and loss-of-function experiments. Utilizing data from public databases, SHOX2 mRNA levels were found to be elevated in GC tissues compared to normal control, this finding was confirmed by RT-qPCR, western blot analysis, and immune-histochemical analyses. Elevated SHOX2 levels could serve as an independent indicator of poor prognosis in GC patients. Furthermore, SHOX2 levels had a negative correlation with CD8 T cells and CD4 memory activated T cells, and a positive correlation with of M0 macrophages in GC patients. Functional analyses revealed that SHOX2 deficiency notably suppressed GC cell proliferation, migration, and invasion. Additionally, SHOX2 deficiency was shown to suppress stemness in GC cells in vitro and in vivo via inactivating wnt/β-catenin signaling. Collectively, SHOX2 may serve as a prognostic marker for GC patients, and downregulation of SHOX2 could effectively impede GC cell growth and stemness by inactivating the wnt/β-catenin signaling pathway. These findings underscore the potential of SHOX2 as a promising therapeutic target for GC.
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Affiliation(s)
- Xiangyu Chen
- The Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuai Li
- The Department of Oncology, The Affiliated of Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Binghua Sun
- The Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Tong T, Huang M, Yan B, Lin B, Yu J, Teng Q, Li P, Pang J. Hippo signaling modulation and its biological implications in urological malignancies. Mol Aspects Med 2024; 98:101280. [PMID: 38870717 DOI: 10.1016/j.mam.2024.101280] [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: 12/19/2023] [Revised: 03/27/2024] [Accepted: 05/19/2024] [Indexed: 06/15/2024]
Abstract
Although cancer diagnosis and treatment have rapidly advanced in recent decades, urological malignancies, which have high morbidity and mortality rates, are among the most difficult diseases to treat. The Hippo signaling is an evolutionarily conserved pathway in organ size control and tissue homeostasis maintenance. Its downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are key modulators of numerous physiological and pathological processes. Recent work clearly indicates that Hippo signaling is frequently altered in human urological malignancies. In this review, we discuss the disparate viewpoints on the upstream regulators of YAP/TAZ and their downstream targets and systematically summarize the biological implications. More importantly, we highlight the molecular mechanisms involved in Hippo-YAP signaling to improve our understanding of its role in every stage of prostate cancer, bladder cancer and kidney cancer progression. A better understanding of the biological outcomes of YAP/TAZ modulation will contribute to the establishment of future therapeutic approaches.
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Affiliation(s)
- Tongyu Tong
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Mengjun Huang
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Binyuan Yan
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Bingbiao Lin
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, Guangdong, 515041, China
| | - Jiaying Yu
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Qiliang Teng
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Peng Li
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
| | - Jun Pang
- Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China.
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Tan H, Liu J, Li Y, Mi Z, Liu B, Rong P. CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway. Cancer Cell Int 2024; 24:124. [PMID: 38570766 PMCID: PMC10988808 DOI: 10.1186/s12935-024-03318-0] [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: 12/19/2023] [Accepted: 03/29/2024] [Indexed: 04/05/2024] Open
Abstract
BACKGROUND Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it. METHODS A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein-protein interaction studies and mouse xenograft models. RESULTS CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis. CONCLUSION CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.
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Affiliation(s)
- Hongpei Tan
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China
| | - Jiahao Liu
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China
| | - Yanan Li
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China
| | - Ze Mi
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China
| | - Baiying Liu
- Department of Gastrointestinal Surgery, Third Xiangya Hospital, Central South University, Changsha, China.
| | - Pengfei Rong
- Department of Radiology, Third Xiangya Hospital, Central South University, Changsha, 410000, China.
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Liu J, Bian T, She B, Liu L, Sun H, Zhang Q, Zhu J, Zhang J, Liu Y. Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation. BMC Cancer 2024; 24:282. [PMID: 38429660 PMCID: PMC10908052 DOI: 10.1186/s12885-024-12022-1] [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: 07/05/2023] [Accepted: 02/19/2024] [Indexed: 03/03/2024] Open
Abstract
Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.
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Affiliation(s)
- Jian Liu
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Tingting Bian
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
- Medical School of Nantong University, Nantong, 226001, China
| | - Bin She
- Academic Development, Shanghai Methyldia Technology Co. Ltd, Tellgen Corporation, No. 412 Huiqing Road, Shanghai, 201203, China
| | - Lei Liu
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Hui Sun
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Qing Zhang
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China
| | - Jun Zhu
- Department of Cardio-Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, China
| | - Jianguo Zhang
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China.
| | - Yifei Liu
- Department of Pathology, Affiliated Hospital of Nantong University, No 20, Xisi Road, Nantong, 226001, China.
- Medical School of Nantong University, Nantong, 226001, China.
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