脑和肌肉ARNT样蛋白1、周期昼夜节律调节因子2、Notch1、糖原合成酶激酶-3β在结直肠腺癌组织中的表达及意义  

Expression of brain and muscle ARNT-like protein 1,period circadian regulator 2,Notch1,and glycogen synthase kinase-3β in colorectal adenocarcinoma and their clinical significance

作　　者：蒋海涛 杜胜奇 李福青 王红 JIANG Haitao;DU Shengqi;LI Fuqing;WANG Hong(Department of Gastroenterology,Digestive Disease Hospital,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou,China;Department of Gastroenterology,the First People’s Hospital of Jingzhou,Jingzhou 434000,Hubei,China)

机构地区：[1]遵义医科大学附属医院消化病医院/遵义医科大学附属医院消化内科,贵州遵义563000 [2]荆州市第一人民医院消化内科,湖北荆州434000

出　　处：《癌症进展》2023年第8期837-842,共6页Oncology Progress

基　　金：遵义医科大学附属医院硕士科研启动基金项目(院字【2017】51号)。

摘　　要：目的探讨脑和肌肉ARNT样蛋白1(BMAL1)、周期昼夜节律调节因子2(PER2)、Notch1、糖原合成酶激酶-3β(GSK-3β)在结直肠腺癌组织中的表达及意义。方法实时荧光定量逆转录聚合酶链反应(RT-PCR)检测11例结直肠癌患者手术切除的新鲜结直肠癌组织及相应癌旁组织中BMAL1、PER2、Notch1、GSK-3βmRNA的相对表达量;免疫组化法检测50例手术切除的结直肠腺癌及癌旁组织、30例经内镜切除的结直肠腺瘤组织中BMAL1、PER2、Notch1、GSK-3β蛋白的表达情况。结果结直肠癌组织中,BMAL1、PER2 mRNA的相对表达量均低于癌旁组织,差异均有统计学意义(P﹤0.05);结直肠癌组织和癌旁组织中Notch1、GSK-3βmRNA的相对表达量比较,差异均无统计学意义(P﹥0.05)。免疫组化结果显示,结直肠腺癌组织、结直肠腺瘤组织及结直肠腺癌癌旁组织中,BMAL1、PER2的表达呈递增趋势,而Notch1、GSK-3β的表达呈递减趋势。淋巴结转移、TNM分期为Ⅲ~Ⅳ期结直肠腺癌患者结直肠腺癌组织中BMAL1、Notch1蛋白表达均高于无淋巴结转移、TNM分期为Ⅰ~Ⅱ期患者(P﹤0.05);病理类型为黏液腺癌的结直肠腺癌组织中PER2蛋白的表达高于管状腺癌(P﹤0.05),GSK-3β的表达低于管状腺癌(P﹤0.05)。Spearman相关分析结果显示,结直肠癌组织中BMAL1的表达与PER2的表达呈正相关(r=0.332,P=0.018),PER2的表达与GSK-3β的表达呈负相关(r=-0.291,P=0.040),Notch1的表达与GSK-3β的表达呈正相关(r=0.285,P=0.045),其余指标间的表达无相关性。结论BMAL1、Notch信号通路、GSK-3β均可能参与调控结直肠癌的发生、发展过程,且GSK-3β可能与BMAL1和Notch信号通路之间存在相互调控作用。Objective To investigate the expression of brain and muscle ARNT-like protein 1(BMAL1),period circadian regulator 2(PER2),Notch1,glycogen synthase kinase-3β(GSK-3β)in colorectal adenocarcinoma and their clinical significance.Method The relative expression of BMAL1,PER2,Notch1,and GSK-3βmRNA in fresh colorectal cancer tissues and corresponding paracancerous tissues of 11 patients were detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).The expression of BMAL1,PER2,Notch1,and GSK-3βproteins in 50 surgically resected colorectal adenocarcinoma and adjacent tissues,and 30 endoscopically resected colorectal adenomas were detected by immunohistochemical method.Result The relative expression levels of BMAL1,PER2 mRNA in colorectal cancer tissues were lower than those in paracancerous tissues,and the differences were statistically significant(P<0.05).There were no significant differences in the relative expression of Notch1,GSK-3βmRNA between colorectal cancer tissues and paracancerous tissues(P>0.05).The results of immunohistochemistry showed that in colorectal adenocarcinoma tissue,colorectal adenoma tissue,and colorectal adenocarcinoma adjacent tissue,the expression of BMAL1 and PER2 increased,while the expression of Notch1 and GSK-3βdecreased.The expression of BMAL1 and Notch1 proteins in colorectal adenocarcinoma cancer tissues of patients with lymph node metastasis and TNM stage III-IV were higher than those in patients without lymph node metastasis and TNM stage I-II(P<0.05).The expression of PER2 protein in colorectal adenocarcinoma cancer tissues of mucinous adenocarcinoma patients was higher than that in tubular adenocarcinoma(P<0.05),and the expression of GSK-3βwas lower than that in tubular adenocarcinoma(P<0.05).Spearman cor-relation analysis results showed that the expression of BMAL1 in colorectal cancer tissues was positively correlated with the expression of PER2(r=0.332,P=0.018),and the expression of PER2 was negatively correlated with the express

关 键 词：结直肠腺癌 脑和肌肉ARNT样蛋白1 周期昼夜节律调节因子2 NOTCH1 糖原合成酶激酶-3Β 

分 类 号：R735.3[医药卫生—肿瘤]