Objective: To investigate the expression of IGF1R-Ras and RAGE-HMGB1 signaling pathways in colorectal cancer patients with type 2 diabetes mellitus and their significance. Methods: The resected cancer tissues were obtained from 59 patients with colorectal cancer (CRC), including 29 patients with type 2 diabetes mellitus (CRC/DM group) and 30 with CRC alone (CRC group). The expressions of IGF1R, Ras, RAGE and HMGB1 in cancer tissues were detected by immunohistochemistry. The differences between the two groups were compared and the relationship between the expression and clinicopathological characteristics was analyzed. Results: In CRC/DM group, the positive rates of IGF1R and Ras were both 65.5% (19/29), and 51.7% (15/29) patients had IGF1R+ Ras+ immunophenotype, which were significantly higher than those in CRC group [33.3% (10/30), 36.7% (11/30) and 20.0% (6/30); P=0.013, 0.027 and 0.011, respectively]. The expression of IGF1R and Ras in CRC / DM group was positively correlated (r=0.479, P=0.017). The positive rate of RAGE expression in CRC group and CRC/DM group was 70.0% (21/30) and 72.4% (21/29) respectively, and the positive rate of HMGB1 expression was 46.7% (14/30) and 58.6% (17/29) respectively, neither was observed with significant difference (P=0.358 and 0.838). However, the proportion of patients with RAGE+ HMGB1+ immunophenotype in CRC/DM group [55.2% (16/29)] was higher than that in CRC Group [26.7% (8/30)] which was statistically significant (P=0.026), and the expression of both proteins was positively correlated in CRC/DM group (r=0.578, P=0.003). The clinicopathological analysis showed that in both groups the expression of IGF1R, Ras, RAGE and HMGB1 had no correlation with the sex, age, differentiation degree, tumor length, T stage and lymph node metastasis (P>0.05). Conclusion: Both IGF1R-Ras and RAGE-HMGB1 pathways may be involved in the oncogenesis of colorectal cancer in patients with type 2 diabetes.
目的： 了解伴有2型糖尿病的结直肠癌(CRC)患者癌组织中胰岛素样生长因子1受体(IGF1R)－Ras和晚期糖基化终产物受体(RAGE)－高迁移率族蛋白1(HMGB1)通路蛋白的表达特点，并探讨其意义。 方法： 选取行手术切除治疗的59例CRC患者，其中伴有2型糖尿病者29例(CRC/DM组)，单纯CRC患者30例(CRC组)。采用免疫组织化学的方法检测手术切除癌组织中IGF1R、Ras、RAGE和HMGB1的表达，比较两组间表达的差异，分析表达与患者临床病理特征的关系。 结果： CRC/DM组IGF1R和Ras表达的阳性率均为65.5%(19/29),具有IGF1R＋ Ras＋免疫表型的患者占51.7%(15/29)，均明显高于CRC组[分别为33.3%(10/30)、36.7%(11/30)和20.0%(6/30)；P值分别为0.013、0.027和0.011]，二者的表达在CRC/DM组呈正相关(r＝0.479，P＝0.017)。CRC组和CRC/DM组RAGE蛋白表达的阳性率分别为70.0%(21/30)和72.4%(21/29)，HMGB1蛋白表达的阳性率分别为46.7%(14/30)和58.6%(17/29)，差异均无统计学意义(P＝0.358，P＝0.838)。但是CRC/DM组具有RAGE＋ HMGB1＋免疫表型患者所占比例[55.2%(16/29)]明显高于CRC组[26.7%(8/30)] ,差异有统计学意义(P＝0.026)，二者的表达在CRC/DM组呈正相关(r＝0.578，P＝0.003)。临床病理分析结果显示，在CRC组和CRC/DM组癌组织中，IGF1R、Ras、RAGE和HMGB1的表达与患者的性别、年龄、分化程度、肿瘤长径、T分期和淋巴结转移均无相关关系(均P>0.05)。 结论： IGF1R－Ras和RAGE－HMGB1通路可能参与了2型糖尿病患者发生CRC的过程。.
Keywords: Colorectal neoplasms; HMGB1; IGF1R; RAGE; Ras; Type 2 diabetes mellitus.