Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer
- Equal contributors
1 Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, Guangzhou, P.R. China
2 Department of Ophthalmology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University Guangzhou, Guangzhou, P.R. China
3 Gastrointestinal Institute, Sun Yat-Sen University Guangzhou, Guangzhou, P.R. China
4 Department of Colon & Rectum Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University Guangzhou, 26 YuancunErheng Road, Guangzhou, 510655, P.R China
BMC Cancer 2014, 14:568 doi:10.1186/1471-2407-14-568Published: 7 August 2014
A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC.
Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed.
ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p< 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05).
Our results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.