Verma Rohit Kumar, Srivastava Prashant Kumar, Singh Ashutosh
Department of Life Sciences, School of Natural Sciences (SONS), Shiv Nadar Institution of Eminence, Delhi NCR, India.
National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
Sci Rep. 2025 Jan 7;15(1):1090. doi: 10.1038/s41598-024-72679-3.
Inhibin, β, which is also known as INHBA, encodes a protein that belongs to the Transforming Growth factor-β (TGF-β) superfamily, which plays a pivotal role in cancer. Gastrointestinal tract (GI tract) cancer refers to the cancers that develop in the colon, liver, esophagus, stomach, rectum, pancreas, and bile ducts of the digestive system. The role of INHBA in all GI tract cancers remains understudied. By utilizing GEPIA2, which uses transcriptomic data from TCGA, we examined the expression of INHBA across different GI tract cancers. The results revealed consistent upregulation of INHBA in all TCGA GI tract cancers, except for liver hepatocellular carcinoma, where it showed downregulation compared to normal tissues, along with GTEx normal samples. Significant differences in INHBA expression were noted in adenocarcinomas of the colon, pancreas, rectum, and stomach, while no such differences were observed in cholangiocarcinoma and liver cancer. Moreover, a comprehensive bioinformatics analysis has been done to demonstrate that the differences in expression levels are significantly related to pathological tumor stages and prognosis in different GI tract cancers. Mucinous adenocarcinoma, esophageal squamous cell carcinoma, and stomach adenocarcinoma show a higher frequency of INHBA alteration and are primarily linked to mutations and amplifications. DNA methylation, immune infiltration, functional enrichment analysis, the genes associated with INHBA, and survival analysis in all TCGA GI tract cancers have been extensively analyzed. In colon and stomach cancers, increased INHBA expression significantly correlates with poorer overall survival (OS). However, in colon and pancreatic adenocarcinoma, higher expression is significantly associated with worse disease-free survival (DFS). Additionally, INHBA expression exhibited a positive correlation with cancer-associated fibroblasts across all gastrointestinal (GI) tract cancers. The KEGG pathway analysis revealed that INHBA and its interacting proteins are involved in several pathways, including TGF-beta signaling, Signalling pathways regulating pluripotency of stem cells, colorectal cancer, pancreatic cancer, AGE-RAGE signaling, and so on as major pathways. These findings demonstrate that INHBA could serve as a potential biomarker therapeutic target for GI tract cancer.
抑制素β，也称为INHBA，编码一种属于转化生长因子-β（TGF-β）超家族的蛋白质，该超家族在癌症中起关键作用。胃肠道（GI）癌是指在消化系统的结肠、肝脏、食道、胃、直肠、胰腺和胆管中发生的癌症。INHBA在所有胃肠道癌症中的作用仍未得到充分研究。通过利用GEPIA2（其使用来自TCGA的转录组数据），我们检查了INHBA在不同胃肠道癌症中的表达。结果显示，除肝细胞癌外，所有TCGA胃肠道癌症中INHBA均呈一致上调，与正常组织相比，肝细胞癌中INHBA呈下调，与GTEx正常样本情况相同。在结肠、胰腺、直肠和胃的腺癌中，INHBA表达存在显著差异，而在胆管癌和肝癌中未观察到此类差异。此外，已进行了全面的生物信息学分析，以证明表达水平的差异与不同胃肠道癌症的病理肿瘤分期和预后显著相关。黏液腺癌、食管鳞状细胞癌和胃腺癌中INHBA改变的频率较高，且主要与突变和扩增有关。已对所有TCGA胃肠道癌症中的DNA甲基化、免疫浸润、功能富集分析、与INHBA相关的基因以及生存分析进行了广泛分析。在结肠癌和胃癌中，INHBA表达增加与较差的总生存期（OS）显著相关。然而，在结肠和胰腺腺癌中，较高的表达与较差的无病生存期（DFS）显著相关。此外，在所有胃肠道（GI）癌症中，INHBA表达与癌症相关成纤维细胞呈正相关。KEGG通路分析显示，INHBA及其相互作用蛋白参与了多种通路，包括TGF-β信号通路、调节干细胞多能性的信号通路、结直肠癌、胰腺癌、AGE-RAGE信号通路等主要通路。这些发现表明，INHBA可能作为胃肠道癌症的潜在生物标志物治疗靶点。
