Bian Geng, Cao Jie, Li Weiyu, Huang Dabing, Ding Xiping, Zang Xiaodong, Ye Yingquan, Li Ping
Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, Anhui 230022, China.
Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
J Cancer. 2024 May 11;15(11):3596-3611. doi: 10.7150/jca.91842. eCollection 2024.
Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for and experiments, respectively, to further validate the role of ELOVL4. Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, and experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.
胃腺癌（STAD）是全球第五大常见癌症，也是癌症相关死亡的第三大主要原因。癌睾丸抗原（CTA）参与多种癌症的发病机制和发展，并在各种类型的癌症中异常过度表达。本研究旨在开发一种与CTA相关的基因特征（CTARSig）来预测STAD患者的预后，并探索其潜在机制。我们对CTA相关基因进行了差异分析和预后分析，并基于Cox和最小绝对收缩与选择算子构建了一个与CTA相关的特征（CTARSig）以及一个新的列线图来预测STAD患者的预后。CTARSig在外部队列（GSE84437）中进一步得到验证。此外，进行了单变量和多变量Cox回归以及受试者工作特征（ROC）分析，以系统地评估CTARSig。使用单样本基因集富集分析和ESTIMATE来表征STAD患者的肿瘤免疫微环境（TIME）。此外，基因集变异分析、京都基因与基因组百科全书以及基因本体分析揭示了与CTARSig相关的生物学功能和信号通路。最后，分别使用人胃癌细胞系HCG - 27和AGS进行实验，以进一步验证ELOVL4的作用。鉴定出11个与CTA相关的基因来构建CTARSig。Kaplan - Meier曲线、独立预后分析和ROC曲线表明，CTARSig能够更好地预测STAD患者的生存情况。此外，在我们的研究中，我们证明ELOVL4在胃癌组织中上调，其高表达与不良生存相关。另外，实验表明ELOVL4促进STAD细胞的转移和侵袭潜能，提示它可能是STAD的一个潜在治疗靶点。在本研究中，为STAD构建了一种与CTA相关的新特征，这可能是患者预后的良好预测指标。因此，ELOVL4可能是胃癌的一个潜在治疗靶点。本研究为CTA在胃癌中的潜在作用提供了新的见解。
