Yang Jian, Xu Wenqian, Wang Shengyu, Yu Zhu, Feng Yue, Li Da, Chen Junqiang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, Guangxi Zhuang Autonomous Region, China.
BMC Cancer. 2025 Jul 1;25(1):1109. doi: 10.1186/s12885-025-14519-9.
EGFLAM is a versatile protein widely expressed in multiple human tissues, yet its function in pan-cancer is not fully understood. To investigate the molecular function of EGFLAM, a comprehensive pan-cancer analysis was carried out using several public databases and bioinformatics tools. Ultimately, confirmatory experiments were conducted in vitro with gastric cancer cell lines. The results showed that EGFLAM expression was elevated in multiple cancer types, especially gastric cancer. It also demonstrated prognostic predictive value in several cancer types, suggesting its potential as a prognostic biomarker. The dysregulation of EGFLAM expression observed in certain cancers might be attributed to factors such as promoter methylation changes, mRNA methylation modifications, and genetic alterations of the EGFLAM locus. EGFLAM expression was associated with Immune cell infiltration, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). Single-cell analysis of gastric cancer showed that EGFLAM was predominantly expressed in fibroblast populations. Functional enrichment analyses (GO/KEGG) demonstrated EGFLAM involvement in extracellular matrix receptor interactions and PI3K-AKT signaling pathway. RT‒qPCR confirmed EGFLAM upregulation in gastric cancer specimens compared to normal controls. In vitro functional assays revealed that EGFLAM knockdown significantly suppressed gastric cancer cell proliferation, migration, and invasion while inducing apoptosis. Collectively, our multi-omics analyses delineated EGFLAM's oncogenic functions across cancer types, positioning it as both a promising prognostic biomarker and a potential therapeutic target for gastric cancer.
表皮生长因子样结构域蛋白8(EGFLAM)是一种在多种人体组织中广泛表达的多功能蛋白,但其在泛癌中的功能尚未完全明确。为了研究EGFLAM的分子功能,我们使用了多个公共数据库和生物信息学工具进行了全面的泛癌分析。最终,我们在体外对胃癌细胞系进行了验证性实验。结果表明,EGFLAM在多种癌症类型中表达升高,尤其是在胃癌中。它在几种癌症类型中也显示出预后预测价值,表明其作为预后生物标志物的潜力。在某些癌症中观察到的EGFLAM表达失调可能归因于启动子甲基化变化、mRNA甲基化修饰以及EGFLAM基因座的基因改变等因素。EGFLAM表达与免疫细胞浸润、免疫检查点、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)相关。胃癌的单细胞分析表明,EGFLAM主要在成纤维细胞群体中表达。功能富集分析(GO/KEGG)表明EGFLAM参与细胞外基质受体相互作用和PI3K-AKT信号通路。逆转录定量聚合酶链反应(RT-qPCR)证实与正常对照相比,胃癌标本中EGFLAM上调。体外功能试验表明,敲低EGFLAM可显著抑制胃癌细胞的增殖、迁移和侵袭,同时诱导细胞凋亡。总的来说,我们的多组学分析描绘了EGFLAM在不同癌症类型中的致癌功能,将其定位为一个有前景的预后生物标志物和胃癌的潜在治疗靶点。