Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 21, 2011; 17(43): 4779-4786
Published online Nov 21, 2011. doi: 10.3748/wjg.v17.i43.4779
Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer
Gui-Fang Guo, Wen-Qi Jiang, Bei Zhang, Yu-Chen Cai, Rui-Hua Xu, Xu-Xian Chen, Fang Wang, Liang-Ping Xia
Gui-Fang Guo, Wen-Qi Jiang, Bei Zhang, Yu-Chen Cai, Rui-Hua Xu, Xu-Xian Chen, Fang Wang, Liang-Ping Xia, State Key Laboratory of Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China
Gui-Fang Guo, Bei Zhang, Xu-Xian Chen, Fang Wang, Liang-Ping Xia, VIP Region, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China
Wen-Qi Jiang, Rui-Hua Xu, Medical Oncology Department, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong Province, China
Author contributions: Guo GF, Jiang WQ, and Xia LP designed the research; Guo GF, Cai YC, Chen XX and Wang F performed the research; Zhang B and Xu RH analyzed the data; Guo GF wrote the paper and Xia LP revised the paper.
Supported by Grants from Science and Technology Planning Project of Guangdong Province, China, No. 2010B031600317; Administration of Traditional Chinese Medicine of Guangdong Province, China, No. 20111169; National Natural Science Foundation of China, No. 81071872
Correspondence to: Liang-Ping Xia, Associated Professor of Medicine, State Key Laboratory of Oncology, Cancer Center, Sun Yat-Sen University, 651 East Dongfeng Road, Guangzhou 510060, Guangdong Province, China. xialiangping@163.com
Telephone: +86-20-87343107 Fax: +86-20-87343392
Received: July 7, 2011
Revised: September 14, 2011
Accepted: October 27, 2011
Published online: November 21, 2011
Abstract

AIM: To investigate the utility of Beclin-1 and LC3, two autophagy-related proteins, in predicting the cetuximab efficacy in advanced colorectal cancer (ACRC).

METHODS: The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1, 2005 to December 31, 2008 were studied, including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy. Beclin-1 and LC3 expression was evaluated by immunohistochemistry, and KRAS status was evaluated by polymerase chain reaction.

RESULTS: Beclin-1 and LC3 expression in ACRC was significantly correlated (r = 0.44, P < 0.01); however, LC3 was more highly expressed in cancerous tissues than in normal tissues (Z = -2.63, P < 0.01). In the cetuximab-containing chemotherapy group, patients with low LC3 expression had higher objective response rates (ORRs) than those with high LC3 expression (52.9% vs 17.9%, P = 0.01), and patients with low Beclin-1 expression had a longer median progression-free survival (PFS) than their counterparts with higher Beclin-1 expression (9.0 mo vs 3.0 mo, P = 0.01). However, neither of these predictive relationships was detected in the group treated with non-cetuximab-containing chemotherapy. Patients with wild-type KRAS had higher ORRs (42.3% vs 9.1%, P = 0.049) and disease control rates (DCRs) (73.1% vs 36.4%, P = 0.035), and longer median PFS (5.5 mo vs 2.5 mo, P = 0.02) than those with mutant KRAS in the cetuximab-containing chemotherapy group. Neither Beclin-1 (P = 0.52) nor LC3 (P = 0.32) expression was significantly correlated with KRAS status.

CONCLUSION: Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression, and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.

Keywords: Beclin-1; Cetuximab; Colorectal neoplasms; Drug therapy; LC3