Literature DB >> 22147978

Autophagy-related proteins Beclin-1 and LC3 predict cetuximab efficacy in advanced colorectal cancer.

Gui-Fang Guo1, Wen-Qi Jiang, Bei Zhang, Yu-Chen Cai, Rui-Hua Xu, Xu-Xian Chen, Fang Wang, Liang-Ping Xia.   

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.

Entities:  

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

Mesh:

Substances:

Year:  2011        PMID: 22147978      PMCID: PMC3229626          DOI: 10.3748/wjg.v17.i43.4779

Source DB:  PubMed          Journal:  World J Gastroenterol        ISSN: 1007-9327            Impact factor:   5.742


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