糖酵解代谢相关蛋白甲基转移酶样3在可切除原发性肝癌组织中的表达及评估预后的价值  

Expression and prognostic value of glycolytic metabolism related protein methyltransferase-like 3 in resectable primary liver cancer

作　　者：赵昌翔 郭力硕 冉辰辰 陈洲 Zhao Changxiang;Guo Lishuo;Ran Chenchen;Chen Zhou(Department of General Surgery,Chongqing Armed Police Corps Hospital,Chongqing 400000,China)

机构地区：[1]中国人民武装警察部队重庆市总队医院普外科,重庆400000

出　　处：《中国医师进修杂志》2022年第11期1030-1037,共8页Chinese Journal of Postgraduates of Medicine

摘　　要：目的探讨糖酵解代谢相关蛋白甲基转移酶样3(METTL3)在可切除原发性肝癌组织中的表达及其评估预后的价值。方法从癌症基因组图谱(TCGA)数据库中下载364例原发性肝癌患者肝癌组织和50例健康人正常肝组织METTL3 mRNA表达数据、临床病理数据和预后信息,并进行基因集富集分析。再选取2016年1月至2019年5月中国人民武装警察部队重庆市总队医院239例接受根治性肝切除术的原发性肝癌患者的组织标本,其中110例含有相配对的癌旁正常肝组织,采用免疫组织化学染色方法检测METTL3蛋白表达。绘制Kaplan-Meier生存曲线,比较采用log-rank检验;采用Cox比例风险模型评估影响原发性肝癌患者预后的危险因素。结果TCGA数据库分析结果显示,肝癌组织METTL3 mRNA表达水平明显高于正常肝组织[3.72(3.19,4.03)比2.45(2.11,2.68)],差异有统计学意义(P=0.007);Kaplan-Meier生存曲线分析结果显示,METTL3 mRNA高表达患者中位总生存时间和无病生存时间明显短于低表达患者(43.0个月比72.0个月和22.0个月比38.0个月,HR=1.7和1.4,P=0.002和0.024)。基因集富集分析结果显示,METTL3 mRNA表达与糖代谢受损有关。在临床样本研究中,肝癌组织METTL3蛋白阳性表达率明显高于癌旁正常肝组织[54.55%(60/110)比14.55%(16/110)],差异有统计学意义(χ^(2)=38.92,P<0.01)。239例原发性肝癌患者中,肝癌组织METTL3蛋白阳性表达132例(55.23%),阴性表达107例。与METTL3蛋白阴性患者相比,阳性患者体质量指数更大,TNM分期、BCLC分期和组织分级更高,病灶更多,肿瘤更大,卫星结节更常见,白细胞计数、血小板计数和中性粒细胞计数更高,差异有统计学意义(P<0.05或<0.01)。Kaplan-Meier生存曲线分析结果显示,METTL3蛋白阳性患者中位总生存时间和无病生存时间明显短于阴性患者(18.0个月比38.0个月和13.0个月比27.0个月,P<0.01)。单因素和多因素Cox分析结果显示,肝癌组织METTL3�Objective To investigate the expression and prognostic value of glycolytic metabolism related methyltransferase-like 3(METTL3)in resectable primary liver cancer.Methods The METTL3 mRNA expression data,clinicopathological data and prognostic information of 364 patients with primary liver cancer and 50 healthy normal liver tissues were downloaded from the Cancer Genome Atlas(TCGA)database,and gene set enrichment analysis was performed.Then the tissue samples of 239 patients with primary liver cancer who underwent radical hepatectomy in Chongqing Armed Police Corps Hospital from January 2016 to may 2019 were selected.Among them,110 cases contained matched normal liver tissue adjacent to the cancer.The expression of METTL3 protein was detected by immunohistochemical staining.Kaplan-Meier survival curve was drawn,and log-rank test was used for comparison;Cox proportional hazard model was used to evaluate the risk factors affecting the prognosis in patients with primary liver cancer.Results TCGA database analysis result showed that the expression level of METTL3 mRNA in liver cancer tissue was significantly higher than that in normal liver tissue:3.72(3.19,4.03)vs.2.45(2.11,2.68),and there was statistical difference(P=0.007);Kaplan-Meier survival curve analysis result showed that the median overall survival time and disease-free survival time in patients with high expression of METTL3 mRNA were significantly shorter than those in patients with low expression of METTL3 mRNA(43.0 months vs.72.0 months and 22.0 months vs.38.0 months,HR=1.7 and 1.4,P=0.002 and 0.024).Gene set enrichment analysis result showed that METTL3 mRNA was related to impaired glucose metabolism.In the clinical sample study,the positive expression rate of METTL3 protein in liver cancer tissue was significantly higher than that in normal liver tissue adjacent to cancer:54.55%(60/110)vs.14.55%(16/110),and there was statistical difference(χ^(2)=38.92,P<0.01).Among 239 patients with primary liver cancer,132 cases(55.23%)had positive expression of METTL3

关 键 词：肝肿瘤 糖酵解 预后 甲基转移酶样蛋白3 

分 类 号：R735.7[医药卫生—肿瘤]