白细胞介素-6及微卫星不稳定在溃疡性结肠炎相关性结直肠癌中的表达及意义

Expressions and significances of interleukin-6 and microsatellite instability in ulcerative colitis-associated colorectal cancer

目的分析溃疡性结肠炎(UC)相关性结直肠癌(UC-CRC)中白细胞介素-6(IL-6)及微卫星不稳定(MSI)情况并探讨其在UC患者癌变过程中所起的作用。方法回顾性分析了鄂东医疗集团2013年1月至2019年1月期间收治的符合纳入标准的17例UC-CRC患者及55例散发性结直肠癌(SCRC)患者术后病理标本资料并检测其癌组织标本中错配修复(MMR)蛋白hMLH1、hPMS2、hMSH2、hMSH6的表达情况;同时检测30例对照(非UC、UC-CRC、SCRC患者)、43例UC、17例UC-CRC及55例SCRC患者的血清中IL-6水平,并对SCRC及UC-CRC患者的癌组织中IL-6与MMR蛋白表达做相关性分析。结果17例UC-CRC的癌组织标本中出现错配修复基因缺失(dMMR)7例(41.2%),其中hMLH1和hPMS2蛋白表达缺失、hMSH2和hMSH6蛋白表达缺失存在明显相关性(P<0.001);UC-CRC组患者血清中IL-6水平明显高于UC组(t=4.97,P<0.001)及SCRC组(t=5.26,P=0.006)。由于病例数较少,未对UC-CRC癌组织中dMMR与IL-6蛋白表达进行统计学分析,而在SCRC癌组织中未发现dMMR与IL-6蛋白表达有关(rs=0.04,P=0.77)。结论与SCRC类似,MSI同样参与了UC-CRC的发生及发展过程,UC-CRC的MMR蛋白缺失更常见于hMLH1与hPMS2、hMSH2与hMSH6的共同表达缺失,未发现IL-6参与了结直肠癌的MSI相关癌变机制,而从有限的病例初步推测IL-6可能参与了UC-CRC患者MSI的发生。

Objective To analyze expressions of interleukin-6(IL-6)and microsatellite instability(MSI)in ulcerative colitis-associated colorectal cancer(UC-CRC)and investigate role of IL-6 and MSI in carcinogenesis of patients with UC.Methods The postoperative pathological data of patients with UC-CRC and patients with sporadic colorectal cancer(SCRC)admitted by Edong Healthcare Group from January 2013 to January 2019 were analyzed retrospectively.The expressions of MMR proteins,including hMLH1,hPMS2,hMSH2,and hMSH6,were detected by the immunohistochemical method.The serum IL-6 levels of the patients with UC,UC-CRC,SCRC and control patients(nonUC,non-UC-CRC,non-SCRC)were detected.The correlation between the IL-6 and MMR protein expression in the cancer tissue was analyzed.Results There were 43 patients with UC,17 UC-CRC,55 SCRC,and 30 control patients.The total rate of MMR-deficient(dMMR)was 41.2%(7/17)in the patients with UC-CRC.There were significant correlations between the hMLH1 and hPMS2 protein expression deletion and between the hMSH2 and hMSH6 protein expression deletion(P<0.001).The serum level of IL-6 in the patients with UC-CRC was significantly higher than that in the patients with UC(t=4.97,P<0.001)and the patients with SCRC(t=5.26,P=0.006).The dMMR might be associated with the level of IL-6 in the patients with UC-CRC,which wasn’t associated with it in the patients with SCRC(rs=0.04,P=0.77).Conclusions Similar to SCRC,MSI also plays a role in occurrence and development of UC-CRC.dMMR in patient with UC-CRC is more common in co-expression deficiency of hMLH1 and hPMS2,as did hMSH2 and hMSH6.IL-6 is not involved in mechanism of MSI-related canceration of colorectal cancer,but it is speculated that IL-6 might be involved in occurrence of MSI of UC-CRC.