基于癌症基因组图谱数据库评估结直肠癌患者微RNA-17-5p的表达特征和预后价值  

Expression and prognostic value of microRNA-17-5p in patients with colorectal cancer using the cancer genome atlas

作　　者：潘成[1,2] 屈潇 秦环龙[1] PAN Cheng;QU Xiao;QIN Huanlong(Department of General Surgerg,Tenth People’s Hospital of Tongji University,Shanghai 200072,China)

机构地区：[1]同济大学附属第十人民医院普外科,上海200072 [2]南京医科大学连云港临床医学院(连云港市第一人民医院)

出　　处：《上海医学》2019年第11期645-650,共6页Shanghai Medical Journal

基　　金：国家自然科学基金(81730102).

摘　　要：目的探讨结直肠癌(colorectal cancer,CRC)患者微RNA-17-5p(miRNA-17)的表达特征和判断预后的意义。方法通过癌症基因组图谱(the cancer genome atlas,TCGA)数据平台获取CRC患者的miRNA-17测序结果、临床病理资料和随访资料。采用χ~2检验分析miRNA-17与性别(男或女)、年龄(≤60岁或>60岁)、肿瘤TNM分期(Ⅰ/Ⅱ/Ⅲ/Ⅳ期)、肿瘤浸润(T分期)、淋巴结转移(N分期)、远处转移(M分期)、术前癌胚抗原(carcino-embryonic antigen,CEA)水平(≥5μg/L或<5μg/L)间的相关性,采用Kaplan-Meier生存分析和Log-rank检验分析miRNA-17表达水平与CRC患者无病生存期(disease-free survival,DFS)、总生存期(overall survival,OS)的相关性;采用单因素和多因素COX回归分析影响患者DFS和OS的危险因素。结果本研究共纳入612例CRC患者的612个肿瘤组织和11个正常组织样本,其中获取完整随访信息372例,男197例、女175例;miRNA-17高表达190例、低表达182例;平均年龄为(65.66±13.24)岁,平均随访时间为(27.65±21.21)个月。肿瘤组织中miRNA-17表达水平为1061.00±29.24,显著高于正常组织中的82.18±11.40(P<0.001)。术前血清CEA水平增高(≥5μg/L)者的miRNA-17表达水平显著高于正常者(<5μg/L,P=0.009),而两组间性别、年龄、肿瘤TNM分期、肿瘤浸润、淋巴结转移和远处转移的差异均无统计学意义(P值均>0.05)。Kaplan-Meier生存曲线和Log-rank检验分析结果显示,miRNA-17表达水平与CRC患者的DFS和OS均不相关(P值均>0.05)。单因素COX回归分析结果显示,肿瘤浸润[风险比(harzard ratio,HR)=2.838,95%CI为1.134~7.104,P=0.025]、淋巴结转移(HR=2.780,95%CI为1.626~4.752)、远处转移(HR=3.361,95%CI为2.012~5.613)、术前CEA水平(HR=2.530,95%CI为1.510~4.239)和肿瘤TNM分期[Ⅲ期(HR=3.805,95%CI为1.114~13.000)、Ⅳ期(HR=12.090,95%CI为3.631~40.250)]是影响CRC患者DFS和OS的危险因素(P值分别<0.01、0.05)。多因素COX回归分析结果显示,年龄(HR=2.562,95%CI为1.355~4.84Objective To identify the expression patterns of microRNA-17-5 p(miRNA-17)in patients with colorectal cancer(CRC).Methods MicroRNA sequence dataset,clinicopathologic data and clinical outcomes of CRC patients were collected from the cancer genome atlas(TCGA).Chi-square test was used to analyze to the association between miRNA-17 and other clinical characteristics,including gender,age(≤60 or>60 years),TNM stage(Ⅰ/Ⅱ/Ⅲ/Ⅳ),tumor invasion(T stage),lymph node metastasis(N stage),distant metastasis(M stage),and preoperative carcino-embryonic antigen(CEA)level(≥5μg/L or<5μg/L).Kaplan-Meier curves analysis and Log-rank test were performed to evaluate prognostic potentials of miRNA-17 in terms of disease-free survival(DFS)and overall survival(OS).A COX proportional hazard model was used to explore the association of prognostic variables with DFS and OS.Results A total of 612 CRC patients(612 tumor samples and 11 normal samples)were included in this study.Of them,372 patients(197 males,175 females)with complete follow-up information were utilized for further analysis.MicroRNA was highly expressed in 190 patients and lowly expressed in 182 patients.The mean age of these patients was(65.66±13.24)years and the mean duration of follow-up was(27.65±21.21)months.The average expression level of miRNA-17 in tumor samples was significantly lower than that in normal samples(1061.00±29.24 vs.82.18±11.40,P<0.001).The expression of miRNA-17 in patients with preoperative CEA level≥5μg/L was significantly higher than that in those with CEA level<5μg/L(P=0.009).The expression level of miRNA-17 was not associated with gender,age,TNM stage,tumor invasion,lymph node metastasis,or distant metastasis(all P>0.05).Kaplan-Meier curves analysis and Log-rank test indicated that the expression level of miRNA-17 was not associated with DFS or OS in CRC patients(P>0.05).Univariate COX regression analysis indicated that tumor invasion(hazard ratio[HR]=2.838,95%CI:1.134-7.104),lymph node metastasis(HR=2.780,95%CI:1.626-4.752),distan

关 键 词：结直肠肿瘤 预后 癌症基因组图谱 微RNA-17-5p 

分 类 号：R735.34[医药卫生—肿瘤]