摘要
目的 关于lncRNAs作为预测性生物标志物和治疗靶点的研究仍然非常有限。文中旨在筛选出HBV相关肝癌差异表达lncRNA谱,寻找灵敏性高、特异性好的HBV相关肝癌早期诊断分子标志物。方法 从GEO下载HBV相关肝癌芯片数据集GSE55092、GSE19665和GSE84402,筛选出差异表达的lncRNA和mRNA,并对差异基因进行功能分析。收集2019年2月至2020年12月右江民族医学院附属医院肝胆外科及体检科患者。肿瘤组(n=45)为HBV阳性原发性肝癌患者,对照组(n=38)为乙肝病毒携带无肿瘤患者。筛选差异表达基因,及HBV相关HCC的候选诊断lncRNA生物标志物,利用DAVID对共表达的差异基因进行GO富集分析及KEGG分析,利用qRT-PCR检测候选lncRNA在血浆样本的相对表达量,通过ROC曲线评价单个血浆lncRNA及与甲胎蛋白联合在HBV相关肝癌诊断中的价值。结果 随机森林的特征变量筛选出上调的AC093642.1、AL445524.1、TRIM52-AS1、EHMT2-AS1、AL356056.2,及下调的AC003991.1、LINC00844、LINC01018、AC008040.1作为HBV相关肝癌的候选诊断性lncRNA生物标志物。候选lncRNA与126个mRNA存在共表达,共199个mRNA-lncRNA共表达对。共表达mRNA的GO功能富集结果表明,表达失调的基因主要富集于与单羧酸代谢过程、类固醇代谢过程、细胞分裂、有丝分裂细胞周期过程等。KEGG通路分析显示,差异基因主要富集在p53信号通路、视黄醇代谢、PI3K-Akt信号通路、化学致癌作用和过氧化物酶体等信号通路。AC003991.1、AL445524.1、LINC00844、AL56056.2、AC008040.1、TRIM52-AS1、LINC01018肿瘤组与对照组比较差异有统计学意义,肿瘤组表达上调(P<0.05)。ROC曲线分析结果显示,AC003991.1、AL445524.1、LINC00844和LINC01018 4种lncRNA联合构建logistic回归模型的AUC为0.910,敏感度和特异度分别为0.828、0.911;4-lncRNA与甲胎蛋白联合构建logistic回归模型的AUC为0.986,敏感度和特异度分别为0.969、0.964。结论 血浆lncRNA
Objective Studies on lncRNAs as predictive biomarkers and therapeutic targets are still very limited. This study aims to screen out differentially expressed lncRNA profiles of HBV-associated liver cancer and search for molecular markers with high sensitivity and good specificity for the early diagnosis. Methods HBV-related liver cancer chip data sets GSE55092, GSE19665 and GSE84402 were downloaded from GEO, and differentially expressed lncRNA and mRNA were screened out, and the differentially expressed genes were analyzed.Patients from the Department of Hepatobiliary Surgery and the Department of Physical Examination in The Affiliated Hospital of Youjiang Medical University for Nationalities from February 2019 to December 2020 were collected. The tumor group(n=45) were HBV-positive primary liver cancer patients, and the control group(n=38) were HBV-carrying patients without tumor.Screening differentially expressed genes and candidate diagnostic lncRNA biomarkers for HBV-associated HCC, DAVID was used to perform GO enrichment analysis and KEGG analysis for co-expressed differentially expressed genes, and qRT-PCR was used to detect the relative expression levels of candidate lncRNA in plasma samples. ROC curve was used to evaluate the value of single plasma lncRNA and its combination with single fetal protein in the diagnosis of HBV-associated liver cancer.Results The up-regulated AC093642.1, AL445524.1, TRIM52-AS1, EHMT2-AS1, AL356056.2 were screened from the characteristic variables of random forest. And down-regulated AC003991.1, LINC00844, LINC01018, AC008040.1 as candidate diagnostic lncRNA biomarkers for HBV-related liver cancer.The candidate lncRNA were co-expressed with 126 mRNA pairs and 199 mRNA-lncRNA pairs. The GO enrichment results of co-expressed mRNA showed that the genes with disregulated expression were mainly enriched in monocarboxylic acid metabolism, steroid metabolism, cell division, mitotic cell cycle, etc.KEGG pathway analysis showed that the differential genes were mainly enriched in p53 sig
作者
农顺强
陈晓昊
许桂丹
韦武均
彭彬
周律
邓益斌
NONG Shun-qiang;CHEN Xiao-hao;XU Gui-dan;WEI Wu-jun;PENG Bin;ZHOU Lü;DENG Yi-bin(Department of Clinical Laboratory,Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,Gugangxi,China)
出处
《医学研究生学报》
CAS
北大核心
2022年第4期376-382,共7页
Journal of Medical Postgraduates
基金
广西壮族自治区自然科学基金(2018GXNSFAA281187)
广西壮族自治区科技计划人才与基地项目(桂科AD17129025)。
