缺氧诱导因子HIF-1α与自噬相关因子Beclin-1和P62在结直肠腺瘤与腺癌癌变中的表达

Expression of hypoxia-inducible factor-1αand autophagy related factors Beclin-1 and P62 in colorectal adenoma canceration

目的探索缺氧诱导因子(HIF-1α)与自噬相关因子(Beclin-1)和(P62)在结直肠息肉、结直肠癌(CRC)中表达及与临床病理特征之间的关系。方法收集2018年1月至2021年1月合肥市第三人民医院结直肠息肉(包括非腺瘤性和腺瘤性息肉)、结直肠癌患者资料和肠镜标本组织,另取正常患者结直肠粘膜作为对照组。苏木精-伊红(HE)染色并根据肠组织进行病理分型,免疫组织化学方法检测HIF-1α和Beclin-1、P62在息肉、癌组织以及正常肠黏膜表达情况并结合其临床病理资料进行统计分析。共51例患者,男性25例,女性26例,中位年龄58.7±13.9(28~95)岁。其中,腺瘤性息肉14例、非腺瘤性息肉16例、CRC11例及正常结直肠黏膜10例。结果HIF-1α在正常结直肠黏膜、非腺瘤性息肉、腺瘤性息肉以及CRC中阳性表达率分别为20.0%、31.2%、64.3%和81.8%;Beclin-1在对应各组阳性率为40.0%、62.5%、85.7%和90.9%;P62在对应各组阳性率为30.0%、56.3%、78.6%和90.9%。与正常组比较,非腺瘤性息肉中HIF-1α、Beclin-1和P62表达差异无统计学意义(P>0.05),但腺瘤性息肉以及CRC中表达差异具有统计意义,呈递增趋势,CRC中表达显著高于腺瘤性息肉和非腺瘤性息肉(P<0.05)。结论HIF‐1α以及自噬相关因子Beclin-1和P62在CRC以及腺瘤性息肉表达显著高于非腺瘤性息肉以及正常结直肠黏膜,呈递增趋势,提示缺氧和自噬功能异常可能参与结直肠腺瘤癌变过程。

Objective To explore the expression of hypoxia-inductive factor(HIF)-1αand autophagy related factors Beclin-1 and P62 in colorectal polyps and cancer.Methods Patients with colorectal polyps(include non-adenomatous polyps and adenomatous polyps)or cancer treated at the Third People's Hospital of Hefei from January 2018 to December 2021 were enrolled,and their clinical data and colorectal tissues were collected.Normal colorectal mucosal samples were included as a control group.The expressions of HIF-1α,Beclin-1,and P62 in polyps,carcinoma,and normal intestinal mucosa were detected by immunohistochemical method,and statistical analysis was performed.Results A total of 51 patients were enrolled,including 25 males and 26 females.The mean age was 58.7±13.9(28~95)years old.There were 14 cases of adenomatous polyps,16 cases of non-adenomatous polyps,11 cases of CRC,and 10 cases of normal colorectal mucosa.The positive expression rates of HIF-1αin normal colorectal mucosa,non-adenomatous polyps,adenomatous polyps,and CRC were 20.0%,31.2%,64.3%,and 81.8%,respectively;the corresponding rates of Beclin-1 were 40.0%,62.5%,85.7%,and 90.9%,and those of P62 were 30.0%,56.3%,78.6%,and 90.9%.The expression of HIF-1α,Beclin-1,and P62 in non-adenomatous polyps showed no significant difference compared with that of the normal group,while the expression of HIF-1α,Beclin-1,and P62 in adenomatous polyps and CRC showed a significant difference compared with that of the normal group.Their expression in CRC was significantly higher than that in adenomatous polyps and non adenomatous polyps(P<0.05).Conclusion The expression of HIF-1αand autophagy related factors Beclin-1 and P62 in is significantly higher in adenomatous polyps and CRC than in non-adenomatous polyps and normal colorectal mucosa,and in CRC than in adenomatous polyps,suggesting that hypoxia and autophagy dysfunction may be involved in the carcinogenesis of colorectal adenoma.