Yang XiaoYing, Wei Mengda, Huang YanQing, Yang Xi, Yuan ZhenMin, Huang JunJie, Wei JunRen, Tian Lei
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Int J Gen Med. 2024 Feb 5;17:471-483. doi: 10.2147/IJGM.S444786. eCollection 2024.
Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear.
The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry.
The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib.
The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.
胃腺癌(STAD)因其诊断时处于晚期且预后较差而构成挑战。整合素亚基α11(ITGA11)编码α整合素,并通过参与细胞增殖和侵袭而与促进肿瘤发生和发展有关。然而,ITGA11在STAD中的精确机制仍不清楚。
检测了来自癌症基因组图谱(TCGA)数据库的375份胃癌样本和32份癌旁组织样本中ITGA11表达水平的差异。使用卡方检验和受试者工作特征(ROC)分析评估ITGA11表达与临床特征之间的关系以及ITGA11的诊断和预后价值。基于ITGA11表达鉴定差异表达基因。随后,使用基因本体论、京都基因与基因组百科全书和基因集富集分析进行功能富集分析。此外,使用CIBERSORT、单样本基因集富集分析和TIMER数据库评估肿瘤患者的免疫浸润和ITGA11相关免疫检查点的表达。使用R oncoPredict软件包分析与ITGA11表达相关的药物敏感性,以指导治疗决策。最后,使用定量PCR(qPCR)和免疫组织化学验证癌组织与相邻组织中ITGA11表达的差异。
与癌旁组织相比,胃癌组织中ITGA11表达显著上调。ITGA11在胃癌(GC)中显示出强大的诊断和预后价值,并且是不良结局的独立危险因素。ITGA11表达水平升高的STAD患者免疫细胞浸润增加,免疫检查点标志物表达增加。值得注意的是,ITGA11表达增加的患者对奥沙利铂和阿法替尼的反应性降低。
结果表明ITGA11在塑造肿瘤免疫微环境中起关键作用,最终在STAD的复杂格局中将ITGA11确立为免疫相关的预后预测指标。