微小染色体维持蛋白复合物6、细胞分裂周期相关蛋白6在肾透明细胞癌组织中的表达及其与恶性生物学行为的相关性研究  

MCM6/CDC6 is a potential biomarker for renal clear cell carcinoma

作　　者：杨拓 蔡科科 赵朋 王金铸 刘立朋 马际春 YANG Tuo;CAI Ke-ke;ZHAO Peng(Department of Urology,Tianjin NanKai Hospital,NanKai University Affiliated NanKai Hospital,Tianjin Key Laboratory of Acute Abdominal Disease Organ Injury and Chinese and Western Medicine Repair,Tianjin 300100,China)

机构地区：[1]天津市中西医结合医院泌尿外科 [2]天津市急腹症器官损伤与中西医修复重点实验室,天津300100

出　　处：《中国中西医结合外科杂志》2024年第5期637-642,共6页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

摘　　要：目的:探讨微小染色体维持蛋白复合物6(MCM6)、细胞分裂周期相关蛋白6(CDC6)在肾透明细胞癌组织中的表达及其与恶性生物学行为的相关性。方法:2021年1月-2023年12月就诊于天津市中西医结合医院泌尿外科的77例肾透明细胞癌患者,选取其癌组织作为研究组,同源远侧的正常肾组织为对照组;基于GEPIA数据库MCM6和CDC6相关信息,应用单克隆抗体免疫组化技术比较研究MCM6和CDC6在肾透明细胞癌组织和正常组织中的表达;采用qRT-PCR和Western Blotting检测shRNA对MCM6表达的影响:应用CCK-8和集落形成试验检测HTB-47和CRL-1932细胞系的体外增殖结果。结果:与正常肾组织相比,MCM6/CDC6在肾透明细胞癌组织中明显上调,且MCM6上调与患者无病生存率降低相关(P<0.05);敲低HTB-47和CRL-1932细胞系的MCM6基因可显著抑制肿瘤细胞的增殖,并显著阻滞了肿瘤细胞分裂周期停留在G2/M期;MCM6的表达与肾癌体积大小显著相关(P=0.010),根据GEPIA数据库显示,CDC6与MCM6有明显的相关性(P<0.01),所有表达结果均通过免疫组化染色检测进一步验证。结论:MCM6的表达上调与肾透明细胞癌的恶性生物学行为和临床进展有关,其可通过影响细胞周期来调控细胞增殖,在肾透明细胞癌组织中,MCM6和CDC6表达量均显著上调且关系密切,表明MCM6/CDC6可能成为预测肾透明细胞癌的潜在生物标记物,并可能成为该病靶向治疗一个新的治疗靶点。Objective To explore the correlation between the expression of MCM6,CDC6 and malignant biological behavior in renal clear cell carcinoma tissues.Methods 77 cases of renal clear cell carcinoma tissue confirmed by pathology were used as the study group,and homologous distal normal renal tissue was used as the control group for the MCM6 and CDC6 study;Based on the GEPIA database,the expression of MCM6 and CDC6 in renal clear cell carcinoma tissue and normal tissue was compared using monoclonal antibody immunohistochemistry technology;qRT-PCR and Western blot were used to detect the effect of shRNA on MCM6 expression:CCK-8 and colony formation assay were used to detect the in vitro proliferation results of HTB-47 and CRL-1932 cell lines.Results Compared with normal renal tissue,MCM6,CDC6 was significantly upregulated in renal clear cell carcinoma tissue,and upregulation of MCM6 was associated with reduced disease-free survival rate(P<0.05);Knocking down the MCM6 gene of HTB-47 and CRL-1932 cell lines can significantly inhibit the proliferation of tumor cells and significantly block the tumor cell division cycle staying in the G2/M phase;The expression of MCM6 was significantly correlated with the volume size of renal cell carcinoma(P=0.010),and according to the GEPIA database,there was a significant correlation between CDC6 and MCM6(P<0.01).All expression results were further validated by immunohistochemical staining.Conclusion The upregulation of MCM6 expression is related to the malignant behavior and clinical progression of renal clear cell carcinoma,which can regulate cell proliferation by affecting the cell cycle.In renal clear cell carcinoma tissues,the expression levels of MCM6 and CDC6 are significantly upregulated and closely related,indicating that MCM6/CDC6 may become a potential biomarker for predicting renal clear cell carcinoma and a new therapeutic target for targeted therapy of this disease.

关 键 词：微小染色体维持蛋白复合物6 细胞分裂周期相关蛋白6 肾透明细胞癌 生物标记物 

分 类 号：R737.11[医药卫生—肿瘤]