A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors.
A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors.
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DOI：
10.1371/journal.pone.0249558
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Mythreye K
中科院分区：
文献类型：
--
作者：
Listik E;Horst B;Choi AS;Lee NY;Győrffy B;Mythreye K
抑制素和激活素是属于TGFβ超家族的二聚体配体，在癌症中具有紧急作用。抑制素含有α亚基（INHA）和β亚基（INHBA或INHB B），而激活素主要是βA（INHBA）或βB（INHB B）亚基的同源二聚体。抑制素是癌症子集中的生物标志物，并且利用辅受体β聚糖（TGFBR 3）和内皮糖蛋白（ENG）用于生理或病理结果。鉴于先前关于癌细胞中的Escherbin、激活素和辅助受体的一系列报道，本研究旨在提供一个全面的分析，使用生物信息学方法评估其在癌症中的功能预后潜力。我们确定了最依赖和影响的癌细胞系和癌症类型，其中包括p53突变的乳腺癌和卵巢癌以及肺腺癌。此外，在多种癌症类型中，INHA本身依赖于TGFBR 3和ENG/CD 105。INHA、INHBA、TGFBR 3和ENG还预测了管腔A型乳腺癌患者对蒽环类和紫杉烷类治疗的反应。我们还获得了一个基因签名模型，可以根据结果对96.7%的病例进行准确分类。最后，我们交叉比较了基因相关性，揭示了INHA对TGFBR 3或ENG的依赖性，这些依赖性影响不同的途径。这些结果表明，在依赖于辅助受体TGFBR 3和ENG的癌症亚组中，EkB蛋白是特别重要的，并且具有实质性的预后价值，从而避免了进一步的研究。
Inhibins and activins are dimeric ligands belonging to the TGFβ superfamily with emergent roles in cancer. Inhibins contain an α-subunit (INHA) and a β-subunit (either INHBA or INHBB), while activins are mainly homodimers of either βA (INHBA) or βB (INHBB) subunits. Inhibins are biomarkers in a subset of cancers and utilize the coreceptors betaglycan (TGFBR3) and endoglin (ENG) for physiological or pathological outcomes. Given the array of prior reports on inhibin, activin and the coreceptors in cancer, this study aims to provide a comprehensive analysis, assessing their functional prognostic potential in cancer using a bioinformatics approach. We identify cancer cell lines and cancer types most dependent and impacted, which included p53 mutated breast and ovarian cancers and lung adenocarcinomas. Moreover, INHA itself was dependent on TGFBR3 and ENG/CD105 in multiple cancer types. INHA, INHBA, TGFBR3, and ENG also predicted patients’ response to anthracycline and taxane therapy in luminal A breast cancers. We also obtained a gene signature model that could accurately classify 96.7% of the cases based on outcomes. Lastly, we cross-compared gene correlations revealing INHA dependency to TGFBR3 or ENG influencing different pathways themselves. These results suggest that inhibins are particularly important in a subset of cancers depending on the coreceptor TGFBR3 and ENG and are of substantial prognostic value, thereby warranting further investigation.
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