Increased Collagen Type V α2 (COL5A2) in Colorectal Cancer is Associated with Poor Prognosis and Tumor Progression

Jie Wang,1,2 Ying-Hua Jiang,1,2 Peng-Yuan Yang,1– 3 Feng Liu1,2 1Minhang Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Medical Systems Biology of School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China; 3Department of Chemistry, Fudan University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Feng LiuMinhang Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-54237451Email liuf@fudan.edu.cnPurpose: Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide with very poor prognosis. Extracellular matrix proteins like collagens play important roles in cancer progression. Collagen type V α 2 (COL5A2) is increased in several cancers but its role in cancer remains unclear.Methods: COL5A2 expression was evaluated by interrogation of public Oncomine gene microarray datasets and immunohistochemistry (IHC) analyses of two tissue microarrays containing 180 paired CRC cases. Survival analysis was performed using Kaplan–Meier survival curve and Cox proportional hazards regression methods. COL5A2 was ectopically expressed in CRC cells, and the cell proliferation was measured using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method.Results: COL5A2 gene was significantly upregulated in the most types of CRC comparing with the normal counterparts. The mRNA expression of COL5A2 was associated with cancer stages, gender, recurrence, microsatellite instability and KRAS status of CRC. COL5A2 protein increased in the cancer epithelial cells comparing with the normal counterpart and associated with age and T stage of CRC, whereas stromal expression of COL5A2 has no significant change between cancerous and normal tissues. COL5A2 gene and protein (epithelial expression) are independent risk factors and predict poor prognosis of CRC. Ectopic expression of COL5A2 drives colon cancer cell growth and upregulates WNT/β-catenin and PI3K/mTOR signaling via binding DDR1.Conclusion: COL5A2 is a potential prognostic marker of CRC.Keywords: colorectal cancer, COL5A2, secreted protein, molecular marker, tissue microarray