摘要
目的 探讨节律基因Bmal1在卵巢癌发生、发展的作用。方法 收集2020年9月至2022年2月经山西医科大学第一医院病理确诊的卵巢浆液性癌病例,分为节律异常组和节律正常组,各30例。检测Bmal1、p53(突变型)、Vimentin在卵巢浆液性癌中的表达,采用实时荧光定量PCR技术(real-time quantitative PCR, RT-qPCR)和蛋白印迹法(Western blot)分别检测两组患者肿瘤组织中Bmal1 mRNA和蛋白的表达,用免疫组织化学法(immunohistochemistry, IHC)检测患者肿瘤组织中p53(突变型)蛋白、Vimentin蛋白的表达,并运用Image-ProPlus软件分析表达强度。运用χ2检验分析节律和临床病理特征的关系。运用Spearman相关性分析Bmal1蛋白和p53(突变型)蛋白、Bmal1蛋白和Vimentin蛋白的表达相关性。结果 节律异常组患者肿瘤组织中Bmal1 mRNA和蛋白的表达低于节律正常组(P<0.000 1),p53(突变型)MOD值和Vimentin MOD值高于节律正常组(P<0.001)。节律异常组高级别卵巢浆液性癌(high grade serous ovarian carcinoma, HGSOC)所占比例、Ⅲ+Ⅳ期者所占比例、有淋巴结转移者所占比例均高于节律正常组(P<0.05);两组<55岁人数所占比例差异无统计学意义。Bmal1 mRNA和蛋白在HGSOC、Ⅲ+Ⅳ期、有淋巴结转移患者中表达分别低于在低级别卵巢浆液性癌(low grade serous ovarian carcinoma, LGSOC)、Ⅰ+Ⅱ期、无淋巴结转移患者中表达(P<0.001);Bmal1 mRNA和蛋白在<55岁和≥55岁患者中表达量差异无统计学意义。Spearman相关性分析显示:Bmal1蛋白和p53(突变型)蛋白表达呈负相关;Bmal1蛋白和Vimentin蛋白表达呈负相关。结论 生物钟节律可以影响Bmal1的表达,Bmal1与卵巢癌患者预后相关。
Objective To investigate the role of rhythm gene Bmal1 in the occurrence and development of ovarian carcinoma.Methods From September 2020 to February 2022,the patients diagnosed pathologically as ovarian serous cancer in the First Hospital of Shanxi Medical University were collected and divided into abnormal rhythm group and normal rhythm group,with 30 cases in each group.Real-time quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of Bmal1 mRNA and protein in tumor tissues in the two groups,and immunohistochemistry(IHC)was used to detect the expression of p53(mutant type)and Vimentin.Image-ProPlus software was used to analyze the expression intensity.Chi square test was used to analyze the relationships between rhythm and clinicopathologic features.Spearman correlation analysis was used to analyze the correlation between Bmal1 protein and p53(mutant)expression,and between Bmal1 protein and Vimentin expression.Results The expression levels of Bmal1 mRNA and protein in tumor tissues in abnormal rhythm group were lower than those in normal rhythm group(P<0.0001).The values of p53(mutant type)MOD and Vimentin MOD in abnormal rhythm group were higher than those in normal rhythm group(P<0.001).The proportions of patients with high grade serous ovarian carcinoma(HGSOC),stageⅢ+Ⅳand lymph node metastasis in abnormal rhythm group were higher than those of patients in normal rhythm group(P<0.05).There was no significant difference in the proportion of patients under 55 years old between the two groups.The levels of Bmal1 mRNA and Bmal1 protein in patients with HGSOC,stageⅢ+Ⅳ,and lymph node metastasis were lower than those of patients with low grade serous ovarian carcinoma(LGSOC),stageⅠ+Ⅱ,no lymph node metastasis(P<0.001).There was no significant difference in the expression levels of Bmal1 mRNA and protein between<55 years old group and≥55 years old group.Spearman correlation analysis showed that the expression of Bmal1 protein was negatively correlated with the expression of p53(mutant)and Vimentin.Conclusion Circadian rhythm can affect the expression of Bmal1.Bmal1 is associated with the prognosis of ovarian cancer patients.
作者
杨展飞
李风艳
王朝霞
YANG Zhanfei;LI Fengyan;WANG Zhaoxia(Department of Obstetrics and Gynecology,First Clinical College of Medicine,Shanxi Medical University,Taiyuan 030001,China;Department of Gynecology,First Hospital of Shanxi Medical University)
出处
《山西医科大学学报》
CAS
2023年第5期573-579,共7页
Journal of Shanxi Medical University
基金
山西省卫健委“四个一批”重点攻关专项资助项目(2021XM36)。
