基于生物信息学探讨miR-15b-5p在头颈部鳞状细胞癌中的诊断价值和潜在作用机制  

Diagnostic value and potential mechanism of miR-15b-5p in head andneck squamous cell carcinoma: an exploration based on bioinformatics

作　　者：苏雪锦 李佰倍 周子燕 陈伟敏 朱明婧 巫兰花 康敏[1,2,3] SU Xuejin;LI Baibei;ZHOU Ziyan;CHEN Weimin;ZHU Mingjing;WU Lanhua;KANG Min(Department of Radiotherapy,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China;Guangxi Regional Key Laboratory of Early Prevention and Treatment of High-Incidence Tumor,Nanning 530021,Guangxi,China;Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases,Nanning 530021,Guangxi,China;Department of Hepatobiliary Surgery,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学第一附属医院放疗科,广西南宁市530021 [2]广西区域性高发肿瘤早期防治研究重点实验室,广西南宁市530021 [3]广西肝病免疫与代谢重点实验室,广西南宁市530021 [4]广西医科大学第一附属医院肝胆外科,广西南宁市530021

出　　处：《广西医学》2023年第23期2861-2871,共11页Guangxi Medical Journal

基　　金：国家自然科学基金(82160467);广西自然科学基金(2023GXNSFDA026009)。

摘　　要：目的采用生物信息学探讨miR-15b-5p在头颈部鳞状细胞癌(HNSCC)中的诊断价值和潜在作用机制。方法(1)从GEO数据库和TCGA数据库中收集HNSCC的miR-15b-5p表达数据和/或HNSCC患者的临床资料。通过Meta分析miR-15b-5p在HNSCC中的表达情况及其诊断HNSCC的价值,使用SPSS 26.0软件分析miR-15b-5p表达水平与HNSCC患者临床特征的关系。利用实时荧光定量PCR检测HNSCC细胞和正常细胞中的miR-15b-5p表达水平。(2)通过miRWalk数据库和GEPIA2数据库分别筛选miR-15b-5p的下游靶基因和HNSCC的差异表达基因,对两者取交集后获得miR-15b-5p在HNSCC中的关键靶基因,对关键靶基因进行富集分析。(3)利用UALCAN数据库分析部分靶基因在HNSCC中的表达水平和甲基化水平。利用GEPIA2数据库分析部分关键靶基因表达情况与HNSCC患者无病生存期和总生存期的关系。结果(1)Meta分析结果显示,miR-15b-5p在HNSCC中呈高表达(P<0.05)。与正常细胞相比,miR-15b-5p在HNSCC细胞中的表达水平升高(P<0.05)。miR-15b-5p表达水平诊断HNSCC的敏感度、特异度、阳性似然比、阴性似然比和诊断优势比分别为0.70、0.72、2.15、0.48和7.33,汇总受试者工作特征曲线下面积为0.81。男性、年龄<60岁、N_(1)~N_(3)期患者的miR-15b-5p表达水平分别高于女性、年龄≥60岁、N_(0)期患者(P<0.05)。(2)共获得54个miR-15b-5p在HNSCC中的关键靶基因。功能富集分析结果提示,关键靶基因与细胞外基质密切相关;通路富集分析结果提示关键靶基因与多条信号通路密切相关,其中包含视黄醇代谢通路。(3)与正常组织相比,关键靶基因RDH12和UGT1A7在HNSCC组织中表达下调,关键靶基因UGT1A10和UGT1A7在HNSCC组织中的甲基化水平降低(P<0.05)。与UGT1A7表达量低的HNSCC患者相比,UGT1A7表达量高的HNSCC患者的无病生存期更长(P<0.05),但两者的总生存期差异无统计学意义(P>0.05)。结论miR-15b-5p与HNSCC的发生、发展密切相�Objective To investigate the diagnostic value and potential mechanism of miR-15b-5p in head and neck squamous cell carcinoma(HNSCC)by using bioinformatics.Methods(1)Expression data of miR-15b-5p in HNSCC and/or clinical data of HNSCC patients were collected from the GEO and TCGA databases.Expression of miR-15b-5p in HNSCC and its value for diagnosing HNSCC were analyzed by Meta-analysis.The SPSS 26.0 software was used to analyze the relation between miR-15b-5p expression and clinical characteristics of HNSCC patients.The real-time fluorescent quantitative PCR was employed to detect miR-15b-5p expression in HNSCC cells and normal cells.(2)The downstream target genes of miR-15b-5p and differentially expressed genes of HNSCC were screened from the databases of miRWalk and GEPIA2,respectively,after performing intersection of the two,the key target genes of miR-15b-5p in HNSCC were obtained.The enrichment analysis was performed on the key target genes.(3)Expressions and methylation levels of partial target genes in HNSCC were analyzed by using the UALCAN database.The relation of expressions of partial key target genes with disease-free survival and overall survival of HNSCC patients was analyzed by employing the GEPIA2 database.Results(1)The results of Meta-analysis revealed that miR-15b-5p exhibited a high expression in HNSCC(P<0.05).Compared with normal cells,expression of miR-15b-5p was elevated in HNSCC cells(P<0.05).The sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and diagnostic odds ratio of miR-15b-5p expression in the diagnosis of HNSCC were 0.70,0.72,2.15,0.48,and 7.33,respectively,and area under the summary receiver operating characteristic curve was 0.81.Male patients,and patients with age<60 years old,in N_(1)-N_(3) stage obtained a higher miR-15b-5p expression as compared with female patients,and patients with age≥60 years old,in N_(0) stage,respectively(P<0.05).(2)A total of 54 key target genes of miR-15b-5p in HNSCC were obtained.The results of functional enrichment anal

关 键 词：头颈部鳞状细胞癌 微小RNA-15b-5p 诊断价值 作用机制 META分析 生物信息学 

分 类 号：R739.6[医药卫生—肿瘤]