Downregulation of Activin A Receptor Type 2A Is Associated with Metastatic Potential and Poor Prognosis of Colon Cancer

Abstract

Aims: Activin A receptor type 2A (ACVR2A) is a membrane receptor in the transforming growth factor- beta (TGF-β signaling pathway, which is involved in the regulation of cell proliferation, migration, and apoptosis. The aim of this study was to examine the expression profiles and biological functions of ACVR2A in colon cancer.

Methods: ACVR2A expression was investigated using the GSE39582 database and two validation cohorts. An in vitro study of cell proliferation and migration of human colon cell lines was also performed.

Results: In the GSE39582 database (n= 497), expression of ACVR2A mRNA was identified as a prognostic factor by linear regression analysis. In one validation cohort of 15 patients with stage IV cancer, the mRNA expression of ACVR2A was significantly reduced in metastatic lesions and primary tumors compared with adjacent normal controls ( P = 0.001). In another validation cohort of tissue microarray (TMA) consisting of 193 cases, reduced ACVR2A protein expression correlated with advanced N stage ( P = 0.001) and positive lymphovascular invasion ( P = 0.005). Strong correlations between low ACVR2A mRNA or protein expression and worse survival were also observed in the GSE39582 database and the TMA validation cohort (all P < 0.05). Moreover, our in vitro studies showed a remarkable increase in cell migration in ACVR2A knockdown cells.

Conclusions: Our findings indicate that loss of ACVR2A has an important role in cancer progression and distant metastasis and may serve as a prognostic marker in patients with colon cancer.