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Expression of Annexin A5 Is Associated With Higher Tumor Stage and Poor Prognosis in Colorectal Adenocarcinomas

Xue, Geng MD*; Hao, Li-Qiang PhD; Ding, Fei-Xiang MD*; Mei, Qian MD*; Huang, Jing-Jing MD*; Fu, Chuan-Gang PhD; Yan, Hong-Li PhD*; Sun, Shu-Han PhD*

Journal of Clinical Gastroenterology: October 2009 - Volume 43 - Issue 9 - p 831-837
doi: 10.1097/MCG.0b013e31819cc731
ALIMENTARY TRACT: Original Articles

Goals To gain an insight into the putative role of annexin A5 (ANXA5) in the tumor stage and its clinical outcome.

Background ANXA5 is a calcium-binding protein, which has been implicated in the carcinogenesis of several carcinomas. However, the role of ANXA5 in colorectal cancer (CRC) is unclear.

Study We investigated the expression of ANXA5 in colorectal adenocarcinoma. This study included 207 consecutive patients with sporadic CRC. Paired colorectal tissue samples and corresponding nonmalignant tissues were obtained by surgical resection. ANXA5 mRNA and protein expression in each tissue were assessed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical staining. Data were statistically correlated with pathologic parameters and clinical outcome.

Results Real-time reverse transcriptase polymerase chain reaction showed that there is an up-regulation in the mRNA level of ANXA5 in tumors (P<0.001). Immunohistochemical study revealed that high ANXA5 expression was present in 40.58% (84 of 207) of tumors. Univariate analysis showed increased ANXA5 expression correlated with pT stage (P=0.008), liver metastasis (P=0.024), pathologic tumor-node–metastasis stage (P=0.015), Dukes' stage (P=0.017), recurrence (P=0.024), cancer-related death (P=0.028), recurrence-free probability (P=0.003), and overall survival (P=0.005). Multivariate analysis showed that ANXA5 expression and liver metastasis significantly correlated with recurrence-free probability (P=0.039 and P=0.048, respectively) and overall survival (P=0.012 and P=0.021, respectively) independent of pT stage and pN stage.

Conclusions From these findings ANXA5 expression seems to be related to the tumor stage and clinical outcome of CRC. Thus ANXA5 could serve as a prognostic marker for tumor progression.

*Department of Medical Genetics, College of Basic Medical Sciences, Second Military Medical University

Department of Colorectal Surgery, Changhai Hospital, Shanghai

Financial Support: This work was funded by National Key Technology R and D Program of China (No. 2006BAI05A05), Natural Science Key Foundation of Shanghai (No. 08ZR1404000), “973” Special Funds for Major State Basic Research of China (No. 2006CB504100), Natural Science Key Foundation of China (No. 30801328), and Key Innovative Research Programs of Shanghai (No. 07DZ1950 and 2006074).

Reprints: Shu-Han Sun, PhD, Department of Medical Genetics, Second Military Medical University, Xiang-Yin Road 800, Shanghai 200433, PR China (e-mail:

Received for publication July 5, 2008; accepted January 16, 2009

Geng Xue and Li-Qiang Hao have contributed equally to this work.

There is no conflict of interest, financial or otherwise, related to the submitted work.

© 2009 Lippincott Williams & Wilkins, Inc.