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Open Access Research article

Expression of A disintegrin and metalloprotease 8 is associated with cell growth and poor survival in colorectal cancer

Zuli Yang1, Yang Bai1, Lijun Huo2, Hao Chen1, Jintuan Huang1, Jizheng Li1, Xinjuan Fan3, Zihuan Yang3, Lei Wang4* and Jianping Wang4*

Author Affiliations

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

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BMC Cancer 2014, 14:568  doi:10.1186/1471-2407-14-568

Published: 7 August 2014

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords:
Colorectal cancer; A disintegrin and metalloprotease 8 (ADAM8); Proliferation; Prognosis; Overall survival; Disease free survival