Insulin-like growth factor receptor-1 overexpression is associated with poor response of rectal cancers to radiotherapy

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(c TNMⅠ-Ⅲ)treated in our department between January 2011and 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 c TNM 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 m RNA 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 m RNA 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.

IGF-1及其受体在直肠癌中的表达和临床意义

[目的]探讨胰岛素样生长因子-1(IGF-1)及其受体IGF-1R蛋白在直肠癌中表达的临床意义。[方法]应用免疫组化SP法检测63例直肠癌样本和30例正常直肠黏膜标本中IGF-1及IGF-1R蛋白的表达,分析直肠癌中IGF-1及IGF-1R蛋白的临床意义。[结果]①IGF-1及IGF-1R蛋白在直肠癌组织中的阳性表达均显著高于正常直肠黏膜组织,差异有统计学意义(P<0.01);②IGF-1及IGF-1R蛋白的表达在直肠癌患者不同年龄、性别、浸润程度和距肛缘距离分组中的差异无统计学意义(P>0.05),但在不同肿瘤分期、肿瘤分化程度和有无淋巴结转移分组中的差异有统计学意义(P<0.01)。[结论]IGF-1及IGF-1R可能参与直肠癌的发生、发展,并与直肠癌的分化和转移有关。