一种用于胃癌预后预测的新型端粒维持基因相关模型。

A Novel Telomere Maintenance Gene-Related Model for Prognosis Prediction in Gastric Cancer.

作者信息

Wang Ke-Liang, Xi Xiao-Xia, Zheng Jian-Hao

机构信息

Department of Gastroenterology, Ningbo No.2 Hospital, No.41, Xibei Street, Ningbo, 315000, Zhejiang, China.

出版信息

Biochem Genet. 2025 May 20. doi: 10.1007/s10528-025-11132-0.

Abstract

Gastric cancer (GC) remains a significant clinical challenge due to its frequent late-stage diagnosis and limited treatment stratification. Telomere maintenance genes (TMGs) are crucial in GC progression, but their prognostic value has not been fully explored. This study is the first to integrate TMGs with machine learning to develop a prognostic model for GC. Using clinical and gene expression data from the TCGA database, differentially expressed genes (DEGs) were identified and intersected with TMGs. Prognostic TMGs were determined through Cox regression and machine learning techniques, including Lasso, random forest, and Xgboost algorithms. A five-gene prognostic model (CCT6A, ELOVL4, PC, PLCL1, RPS4Y1) was developed and validated using TCGA data. The model demonstrated strong predictive performance, with AUCs of 0.71, 0.71, and 0.70 at 1-, 3-, and 5-year survival, respectively. High-risk patients had significantly poorer overall survival (OS). Further analysis of the tumor microenvironment (TME) showed that high-risk patients exhibited increased immune cell infiltration, and TMG-associated pathways such as apoptosis, epithelial-mesenchymal transition (EMT), and IL6/JAK/STAT3 signaling were prominent. High EMT scores were linked to worse prognosis. In addition, the hub genes were upregulated in GC patients and cells, correlating with decreased OS. PLCL1 significantly promoted GC cell proliferation, migration, and invasion, and it also activated the inflammation-related pathways in GC. In conclusion, this study not only highlights the prognostic relevance of TMGs in GC but also underscores the clinical translation potential of the prognostic model, offering novel targets for personalized therapeutic strategies in GC.

摘要

由于胃癌(GC)经常在晚期才被诊断出来且治疗分层有限,它仍然是一个重大的临床挑战。端粒维持基因(TMGs)在GC进展中至关重要,但其预后价值尚未得到充分探索。本研究首次将TMGs与机器学习相结合,以开发一种GC的预后模型。利用来自TCGA数据库的临床和基因表达数据,识别差异表达基因(DEGs)并与TMGs进行交集分析。通过Cox回归和机器学习技术(包括Lasso、随机森林和Xgboost算法)确定预后TMGs。使用TCGA数据开发并验证了一个五基因预后模型(CCT6A、ELOVL4、PC、PLCL1、RPS4Y1)。该模型表现出强大的预测性能,在1年、3年和5年生存率时的曲线下面积(AUC)分别为0.71、0.71和0.70。高危患者的总生存期(OS)明显更差。对肿瘤微环境(TME)的进一步分析表明,高危患者的免疫细胞浸润增加,与TMG相关的途径如凋亡、上皮-间质转化(EMT)和IL6/JAK/STAT3信号通路较为突出。高EMT评分与更差的预后相关。此外,枢纽基因在GC患者和细胞中上调,与OS降低相关。PLCL1显著促进GC细胞的增殖、迁移和侵袭,还激活了GC中与炎症相关的途径。总之,本研究不仅突出了TMGs在GC中的预后相关性,还强调了预后模型的临床转化潜力,为GC的个性化治疗策略提供了新的靶点。

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