Velásquez Sotomayor Mariana Belén, Campos Segura Anthony Vladimir, Asurza Montalva Ricardo José, Marín-Sánchez Obert, Murillo Carrasco Alexis Germán, Ortiz Rojas César Alexander
Immunology and Cancer Research Group (IMMUCA), Lima, Peru.
Escuela de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú.
Front Genet. 2023 Sep 12;14:1206609. doi: 10.3389/fgene.2023.1206609. eCollection 2023.
Gastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consistently associated with prognosis in GC. Based on the ROC curve, patients were categorized into high and low-expression groups for each gene using the best cutoff point. Genes associated with survival (AUC > 0.5; univariate and multivariate Cox regressions, < 0.05) were used to model gene expression-based scores by weighted sum using the pooled Cox β regression coefficients. Cox regression ( < 0.05), AUC > 0.5, sensitivity > 0.5, and specificity > 0.5 were considered to identify the best scores. Gene set enrichment analysis (KEGG, REACTOME, and Gene Ontology databases), as well as microenvironment composition and stromal cell signatures prediction (CIBERSORT, EPIC, xCell, MCP-counter, and quanTIseq web tools) were performed. We found 11 genes related to GC survival in the five independent cohorts. Then, we modeled scores by calculating all possible combinations between these genes. Among the 2,047 scores, we identified a panel based on the expression of seven genes. It was named GES7 and is composed of , , , , , , and genes. GES7 features were validated in two independent external cohorts. Next, GES7 was found to recategorize patients from AJCC TNM stages into a best-fitted prognostic group. The GES7 was associated with activation of the TGF-β pathway and repression of anticancer immune cells. Finally, we compared the GES7 with 30 previous proposed scores, finding that GES7 is one of the most robust scores. As a result, the GES7 is a reliable gene-expression-based signature to improve the prognosis estimation in GC.
胃癌（GC）的发病率在全球排名第五，死亡率排名第四。GC患者的高死亡率需要新的生物标志物来改善生存估计。在本研究中，我们对五个公开可用的队列进行了基于转录组的分析，以鉴定与GC预后始终相关的基因。基于ROC曲线，使用最佳截断点将每个基因的患者分为高表达组和低表达组。使用合并的Coxβ回归系数通过加权和对与生存相关的基因（AUC>0.5；单变量和多变量Cox回归，<0.05）进行建模，以生成基于基因表达的分数。考虑Cox回归（<0.05）、AUC>0.5、敏感性>0.5和特异性>0.5来确定最佳分数。进行了基因集富集分析（KEGG、REACTOME和基因本体数据库），以及微环境组成和基质细胞特征预测（CIBERSORT、EPIC、xCell、MCP-counter和quanTIseq网络工具）。我们在五个独立队列中发现了11个与GC生存相关的基因。然后，我们通过计算这些基因之间的所有可能组合来建模分数。在2047个分数中，我们基于七个基因的表达确定了一个panel。它被命名为GES7，由、、、、、和基因组成。GES7特征在两个独立的外部队列中得到验证。接下来，发现GES7可将AJCC TNM分期的患者重新分类为最适合的预后组。GES7与TGF-β途径的激活和抗癌免疫细胞的抑制有关。最后我们将GES7与之前提出的30个分数进行比较，发现GES7是最稳健的分数之一。因此，GES7是一种可靠的基于基因表达的特征，可改善GC的预后估计。
