Identification of the RP11-21C4.1/SVEP1 gene pair associated with FAT2 mutations as a potential biomarker in gastric cancer

Gastric cancer (GC) is one of the most common malignancies worldwide. Despite rapid advances in systemic therapy, GC remains the third leading cause of cancer-related deaths. We aimed to identify a novel prognostic signature associated with FAT2 mutations in GC. We analyzed the expression levels of FAT2-mutant and FAT2-wildtype GC samples obtained from The Cancer Genome Atlas (TCGA). The Kaplan–Meier survival curve showed that patients with FAT2 mutations showed better prognosis than those without the mutation. Sixteen long non-coding RNAs (lncRNAs) and 62 messenger RNAs (mRNAs) associated with FAT2 mutations were correlated with the prognosis of GC. We then constructed a 4-mRNA signature and a 5-lncRNA signature for GC. Finally, we identified the most relevant RP11-21 C4.1/SVEP1 gene pair as a prognostic signature of GC that exhibited superior predictive performance in comparison with the 4-mRNA or 5-lncRNA signature by weighted gene correlation network analysis (WGCNA) and Cox proportional hazards regression analysis. In this study, we constructed a prognostic signature of GC by integrative genomics analysis, which also provided insights into the molecular mechanisms linked to FAT2 mutations in GC.

胃癌（Gastric cancer, GC）是全球最常见的恶性肿瘤之一。尽管系统治疗领域已取得快速进展，GC仍是癌症相关死亡的第三大诱因。本研究旨在筛选与胃癌FAT2突变相关的新型预后特征。我们对从癌症基因组图谱（The Cancer Genome Atlas, TCGA）中获取的FAT2突变型与FAT2野生型胃癌样本的表达水平进行了分析。卡普兰-迈耶生存曲线（Kaplan–Meier survival curve）结果显示，携带FAT2突变的患者预后优于未发生该突变的患者。本研究共鉴定出16个与FAT2突变相关的长链非编码RNA（long non-coding RNAs, lncRNAs）及62个信使RNA（messenger RNAs, mRNAs），上述分子均与胃癌预后相关。随后，我们分别构建了针对胃癌的4-mRNA预后特征与5-lncRNA预后特征。最后，通过加权基因共表达网络分析（weighted gene correlation network analysis, WGCNA）与Cox比例风险回归分析（Cox proportional hazards regression analysis），我们筛选出关联性最强的RP11-21 C4.1/SVEP1基因对作为胃癌预后特征，其预测性能优于前述4-mRNA与5-lncRNA预后特征。本研究通过整合基因组分析构建了胃癌预后特征，同时为阐明胃癌FAT2突变相关的分子机制提供了新的见解。