J Cancer 2018; 9(19):3626-3633. doi:10.7150/jca.26790

Research Paper

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

Changhua Zhuo1,6, Dan Hu2,7, Jing Li3, Hui Yu1, Xiandong Lin2,7, Ying Chen4, Yong Zhuang1, Qingguo Li5, Xiongwei Zheng2,7, Chunkang Yang1,6✉

1. Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, China
2. Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, China
3. Departments of CyberKnife, Huashan Hospital, Fudan University, Shanghai 200032, China
4. Department of Clinical Laboratory, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, China
5. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
6. Fujian Provincial Key Laboratory of Tumor Biotherapy, Fuzhou 350014, China
7. Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China

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.

Keywords: Activin A Receptor Type 2A (ACVR2A), Colon Cancer, Tissue Microarray, Liver Metastasis, Cell Proliferation, Cell Migration

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How to cite this article:
Zhuo C, Hu D, Li J, Yu H, Lin X, Chen Y, Zhuang Y, Li Q, Zheng X, Yang C. Downregulation of Activin A Receptor Type 2A Is Associated with Metastatic Potential and Poor Prognosis of Colon Cancer. J Cancer 2018; 9(19):3626-3633. doi:10.7150/jca.26790. Available from http://www.jcancer.org/v09p3626.htm