Insulin-Like Growth Factor-1 Receptor Overexpression in Pretreatment Biopsies Predicts Response of Rectal Cancer to Preoperative Radiotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Xiaoyu , YAO Xuequan , CHEN Che , CHEN Zhiwei , XU Zhe , LI Weisu , LIU Fukun.

Department of Digestive Tumor Surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, Jiangsu Province, China;

Corresponding author：

Keywords：

Insulin-like growth factor-1 receptor; Rectal neoplasm; Preoperative radiotherapy; Immunohistochemistry; Reverse transcription-polymerase chain reaction

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ObjectiveTo evaluate the possible role of the expression of insulin-like growth factor-1 receptor (IGF-1R) in determining rectal cancer radiosensitivity. MethodsThe paired preradiation biopsy specimens and postoperative specimens were obtained from 87 patients with rectal cancer in the department of digestive tumor surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2009 to December 2010. The IGF-1R expression was examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). The tumor radiosensitivity was defined according to Rectal Cancer Regression Grade, then the relation between the IGF-1R expression and tumor radiosensitivity was evaluated. ResultsCompared with the preradiation biopsy specimens, IGF-1R expression significantly increased in the paired postoperative specimens of the residual cancer cells (P lt;0.001). The IHC result demonstrated IGF-1R overexpression was significantly associated with a poor response to radiotherapy (rs=0.401, P lt;0.001); RT-PCR detection of IGF-1R expression on preradiation biopsy specimens also showed that IGF-1R mRNA negative patients had a higher radiation sensitivity (rs=0.497, P lt;0.001). ConclusionDetection of IGF-1R expression may predict radiosensitivity of preoperative irradiation for rectal cancer.

Citation： WU Xiaoyu,YAO Xuequan,CHEN Che,CHEN Zhiwei,XU Zhe,LI Weisu,LIU Fukun.. Insulin-Like Growth Factor-1 Receptor Overexpression in Pretreatment Biopsies Predicts Response of Rectal Cancer to Preoperative Radiotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(10): 1069-1073. doi: Copy

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11.	Dittmann KH, Gueven N, Mayer C, et al. The radioprotective effect of BBI is associated with the activation of DNA repairrelevant genes [J]. Int J Radiat Biol, 1998, 74(2): 225230.
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1. 顾晋, 詹天成, 姚云峰. 结直肠癌的新辅助治疗 [J]. 中国普外基础与临床杂志, 2007, 14(6): 628629．.
2. 肖毅．直肠癌新辅助治疗 [J]．中国普外基础与临床杂志, 2010, 17(9): 906909．.
3. 黄桂林, 吴毅平, 雷娜. 胰岛素样生长因子1在原发性结直肠癌中表达的研究 [J]. 中国普外基础与临床杂志, 2009, 16(9): 693697.
4. Yu D, Shibuya H, Miura M. Roles of the insulinlike growth factor Ⅰ receptor Cterminus in cellular radioresistance [J]. Biochem Biophys Res Commun, 2003, 311(1): 174178.
5. Wheeler JM, Warren BF, Mortensen NJ, et al. Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system [J]. Dis Colon Rectum, 2002, 45(8): 10511056.
6. Ross GM. Induction of cell death by radiotherapy [J]. Endocr Relat Cancer, 1999, 6(1): 4144.
7. Komuro Y, Watanabe T, Hosoi Y, et al. Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression [J]. J Exp Clin Cancer Res, 2003, 22(2): 223228.
8. Komuro Y, Watanabe T, Hosoi Y, et al. The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma [J]. Cancer, 2002, 95(6): 11991205.
9. HéronMilhavet L, LeRoith D. Insulinlike growth factor Ⅰ induces MDM2dependent degradation of p53 via the p38 MAPK pathway in response to DNA damage [J]. J Biol Chem, 2002, 277(18): 1560015606.
10. Peruzzi F, Prisco M, Morrione A, et al. Antiapoptotic signaling of the insulinlike growth factorⅠ receptor through mitochondrial translocation of cRaf and Nedd4 [J]. J Biol Chem, 2001, 276(28): 2599025996.
11. Dittmann KH, Gueven N, Mayer C, et al. The radioprotective effect of BBI is associated with the activation of DNA repairrelevant genes [J]. Int J Radiat Biol, 1998, 74(2): 225230.
12. Hofmann F, GarcíaEcheverría C. Blocking the insulinlike growth factorⅠ receptor as a strategy for targeting cancer [J]. Drug Discov Today, 2005, 10(15): 10411047.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Insulin-Like Growth Factor-1 Receptor Overexpression in Pretreatment Biopsies Predicts Response of Rectal Cancer to Preoperative Radiotherapy

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