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使用 STRING、MCODE 和 GEPIA2 构建子宫内膜癌免疫网络及检查点基因的预后评估

英文原题:Immune Network Construction and Prognostic Evaluation of Checkpoint Genes in Endometrial Cancer Using STRING, MCODE, and GEPIA2.

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Immune Network Construction and Prognostic Evaluation of Checkpoint Genes in Endometrial Cancer Using STRING, MCODE, and GEPIA2.

PubMed 2026/03/01(内容时间) Cancer Diagn Progn

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研究概要

该计算机模拟免疫网络突出了以检查点为中心的枢纽以及在子宫内膜癌中具有预后相关性的协调免疫程序,为生物标志物指导的免疫治疗开发和患者分层提供了依据。需要在独立队列中进行验证,并与临床病理及治疗反应数据进行关联,以支持临床转化。

研究思路结论见上方概要

子宫内膜癌(EC)是女性重要的健康问题,免疫治疗正成为晚期病例的一种有前景的选择。TIL(肿瘤浸润淋巴细胞)(TILs)和免疫检查点,包括PDCD1、CD274和PDCD1LG2,日益被认为是预后标志物。本研究旨在利用STRING、MCODE和GEPIA2构建计算机模拟免疫网络,并评估检查点基因在EC中的预后影响。

回顾性分析使用 TCGA-UCEC(癌症基因组图谱-子宫体子宫内膜癌)和 GTEx 数据集,并报告了免疫相关基因。在 STRING v12.0 中分析基因(置信度 ≥0.7;每个节点最多 10 个邻居)以生成蛋白质-蛋白质相互作用(PPI)网络,导出至 Cytoscape v3.10.2,并用 MCODE 处理以识别功能簇。在 GEPIA2 中使用基于中位数的分层和 log-rank 检验(p <0.05)评估枢纽基因的表达和总生存期(OS)。在 TIMER2.0 中评估了六种免疫特征。PDCD1 和 CD274 与其他免疫效应因子显示出强相互作用。

CD40 下调和 LGALS9 上调,分别不影响 OS。CTLA4、PDCD1、TIGIT、CD8A、CD8B、GZMB、PRF1、TBX21、FOXP3、CXCL9、CD28 和 ICOS 的联合过表达与 OS 改善相关,提示直接免疫效应和靶向治疗反应增强。

展开英文摘要原文

Retrospective analysis used TCGA-UCEC (The Cancer Genome Atlas - Uterine Corpus Endometrial Carcinoma) and GTEx datasets and reported immune-related genes. Genes were analyzed in STRING v12.0 (confidence ≥0.7; up to 10 neighbors per node) to generate a protein-protein interaction (PPI) network, exported to Cytoscape v3.10.2, and processed with MCODE to identify functional clusters. Hub genes were evaluated for expression and overall survival (OS) in GEPIA2 using median-based stratification and log-rank tests ( p <0.05). Six immune signatures were assessed in TIMER2.0. PDCD1 and CD274 showed strong interactions with other immune effectors.

CD40 and LGALS9 were down- and upregulated, respectively, without affecting OS. Combined overexpression of CTLA4 , PDCD1 , TIGIT , CD8A , CD8B , GZMB , PRF1 , TBX21 , FOXP3 , CXCL9 , CD28 , and ICOS correlated with improved OS, suggesting direct immune effects and enhanced responses to targeted therapies.

This in silico immune network highlights checkpoint centered hubs and coordinated immune programs with prognostic relevance in endometrial cancer, providing a rationale for biomarker guided immunotherapy development and patient stratification. Validation in independent cohorts and correlation with clinicopathologic and treatment response data are needed to support clinical translation.

论文信息

作者
Ribeiro DA Costa REA、Zeferino LC、Teixeira JC
第一作者单位
Obstetrics and Gynecology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.Brazil
通讯作者单位
Department of Tocogynecology, Faculty of Medical Sciences of the State University of Campinas, Campinas, Brazil.Brazil
期刊
Cancer diagnosis & prognosis2026 Mar-Apr
原文标识
PubMed 41778235 · DOI 10.21873/cdp.10532