Retrospective Study
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World J Gastroenterol. Nov 21, 2014; 20(43): 16268-16274
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16268
Insulin-like growth factor receptor-1 overexpression is associated with poor response of rectal cancers to radiotherapy
Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Gang Li
Xiao-Yu Wu, Zhen-Feng Wu, Qin-Hong Cao, Che Chen, Zhi-Wei Chen, Zhe Xu, Wei-Su Li, Fu-Kun Liu, Xue-Quan Yao, Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Gang Li, Department of General Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu Province, China
Author contributions: Wu XY and Wu ZF contributed equally to this work; Wu XY and Wu ZF designed research; Wu XY and Wu ZF performed research; Cao QH and Chen ZW contributed new reagents or analytic tools; Wu ZF analyzed data; Wu XY wrote the paper; all the authors contributed to this paper.
Supported by The National Natural Science Foundation of China, No. 81402523 to Wu XY and No. 81201797 to Li G
Correspondence to: Gang Li, MD, Department of General Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing 210009, Jiangsu Province, China. searain@sohu.com
Telephone: +86-25-86600460 Fax: +86-25-86600460
Received: January 27, 2014
Revised: May 2, 2014
Accepted: July 16, 2014
Published online: November 21, 2014
Abstract

AIM: To explore the potential correlation between insulin-like growth factor receptor-1 (IGF-1R) expression and rectal cancer radiosensitivity.

METHODS: Eighty-seven rectal cancer patients (cTNM I-III) treated in our department between January 2011 and December 2012 were enrolled. All subjects were treated with preoperative radiotherapy and radical resection of rectal carcinoma. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to detect IGF-1R expression in pre-treatment and postoperative colorectal cancer specimens. Radiosensitivity for rectal cancer specimens was evaluated by observing rectal carcinoma mass regression combined with fibrosis on HE staining, degree of necrosis and quantity of remaining tumor cells. The relative IGF-1R expression was evaluated for association with tumor radiosensitivity.

RESULTS: Immunohistochemistry showed diffuse IGF-1R staining on rectal cancer cells with various degrees of signal density. IGF-1R expression was significantly correlated with cTNM staging (P = 0.012) while no significant association was observed with age, sex, tumor size and degree of differentiation (P = 0.424, 0.969, 0.604, 0.642). According to the Rectal Cancer Regression Grades (RCRG), there were 31 cases of RCRG1 (radiation sensitive), 28 cases of RCRG2 and 28 cases of RCRG3 (radiation resistance) in 87 rectal cancer subjects. IGF-1R protein hyper-expression was significantly correlated with a poor response to radiotherapy (P < 0.001, r = 0.401). RT-PCR results from pre-radiation biopsy specimens also showed that IGF-1R mRNA negative group exhibited a higher radiation sensitivity (P < 0.001, r = 0.497). Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly increased IGF-1R protein and mRNA expression in the residual cancer cells (P < 0.001, respectively).

CONCLUSION: IGF-1R expression level may serve as a predictive biomarker for radiosensitivity of rectal cancer before preoperative radiotherapy.

Keywords: Insulin-like growth factor-1 receptor, Rectal carcinoma, Preoperative radiotherapy, Immunohistochemistry, Reverse transcription-polymerase chain reaction

Core tip: This was the first report examining the relation between insulin-like growth factor receptor-1 (IGF-1R) expression and radiosensitivity in rectal cancer. Results showed that IGF-1R hyperexpression is significantly associated with poor response to radiotherapy. Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly increased IGF-1R expression in the residual cancer cells.