A meta-analysis of the inhibin network reveals prognostic value in multiple solid tumors

Abstract

ABSTRACTInhibins 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 (eitherINHBAorINHBB), 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,INHAitself was dependent onTGFBR3andENGin multiple cancer types.INHA,INHBA,TGFBR3,andENGalso 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 revealingINHAdependency toTGFBR3orENGinfluencing different pathways themselves. These results suggest that inhibins are particularly important in a subset of cancers depending on the coreceptorTGFBR3andENGand are of substantial prognostic value, thereby warranting further investigation.