Ding Jing, Li Cong, Tang Jie, Yi Cheng, Liu Ji-Yan, Qiu Meng
Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan Province, 610041, China.
Pathol Oncol Res. 2016 Oct;22(4):773-9. doi: 10.1007/s12253-016-0065-6. Epub 2016 May 2.
Preexisting type 2 diabetes mellitus (preDM) increases occurrence and mortality of colorectal cancer (CRC). Insulin growth factor (IGF)/insulin receptor (IR) axes play an important role in the development of both diabetes and CRC. We aimed to explore the characteristics of proteins expression in IGF/IR axes in CRC tissues with preDM. Two hundred fifty CRC patients in West China hospital were included in analysis. Among them, 125 patients had history of diabetes matched by 125 CRC without diabetes at a 1:1 ratio. Immunohistochemical staining was used to detect the expression of proteins in IGF/IR axis. More positive expression of IGF-1, IGF-1R and IR were found in CRC group with diabetes than in non-diabetes group. No difference was detected in the expression of IR substrate-1, IR substrate-2, IGF-2, IGF binding protein 3, and mammalian target of rapamycin between two groups. Multivariate analysis showed that diabetes history was associated with all of the expression of IGF-1, IGF-1R and IR, and higher T staging and lymph node metastasis were respectively independent factors of IGF-1 and IGF-1R expression in CRC patients. Besides, IGF-1 expression was positively associated with IGF-1R and IR expression in all CRC tissues, and the association of IGF-1 and IR expression seemed to be closer in diabetes group than in non-diabetes group. Higher expression of IGF-1, IGF-1R and IR proteins in CRC was associated with diabetes, suggesting IGF-1/IR signaling may play a special part in development of CRC in patients with diabetes.
既往2型糖尿病（preDM）会增加结直肠癌（CRC）的发生率和死亡率。胰岛素生长因子（IGF）/胰岛素受体（IR）轴在糖尿病和结直肠癌的发生发展中均起重要作用。我们旨在探讨合并preDM的CRC组织中IGF/IR轴蛋白表达的特征。纳入了华西医院的250例CRC患者进行分析。其中，125例有糖尿病史的患者与125例无糖尿病的CRC患者按1:1比例匹配。采用免疫组织化学染色检测IGF/IR轴蛋白的表达。糖尿病CRC组中IGF-1、IGF-1R和IR的阳性表达高于非糖尿病组。两组间IR底物-1、IR底物-2、IGF-2、IGF结合蛋白3和雷帕霉素哺乳动物靶点的表达无差异。多因素分析显示，糖尿病史与IGF-1、IGF-1R和IR的所有表达均相关，较高的T分期和淋巴结转移分别是CRC患者中IGF-1和IGF-1R表达的独立因素。此外，在所有CRC组织中，IGF-1表达与IGF-1R和IR表达呈正相关，且糖尿病组中IGF-1与IR表达的相关性似乎比非糖尿病组更密切。CRC中IGF-1蛋白、IGF-1R蛋白和IR蛋白的高表达与糖尿病相关，提示IGF-1/IR信号通路可能在糖尿病患者CRC的发生发展中起特殊作用。
