LINC01465在痛风性关节炎中的表达及临床意义

doi:10.16138/j.1673-6087.2023.02.006

摘要/Abstract

摘要：

目的: 探索痛风性关节炎（gouty arthritis，GA）潜在发病相关长链非编码RNA（long noncoding RNA, lncRNA）及与炎症因子的相关性。方法: 通过基因表达综合（Gene Expression Omnibus, GEO）数据库获取GA芯片数据，通过多种机器学习方法筛选并取交集得到关键的lncRNA。分析与lncRNA共表达的mRNA，并进行GO富集分析及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）信号通路分析。通过实时荧光定量PCR（quantitative real-time polymerase chain reaction, qRT-PCR）验证关键lncRNA在GA患者中表达情况与炎症因子水平相关性，并绘制受试者操作特征曲线（receiver operator characteristic curve，ROC曲线）分析LINC01465表达水平对GA患者诊断价值。结果: 筛选出GA关键lncRNA 1个（LINC01465）。GO富集分析结果显示富集于RNA剪接、氧化磷酸化、还原型烟酰胺腺嘌呤二核苷酸（reduced nicotinamide adenine dinucleotide，NADH）脱氢酶活性等功能。KEGG信号通路分析显示主要富集于烟酸和烟酰胺代谢、磷脂酰肌醇3激酶（phosphoinositide 3-kinase，PI3K）-Akt、肿瘤坏死因子信号等代谢及炎症通路。qRT-PCR结果显示在GA患者中LINC01465表达上调，与红细胞沉降率（r=0.658，P=0.030）、C反应蛋白（r=0.660，P=0.040）、白介素-6（r=0.794，P=0.008）表达呈正相关。ROC曲线下面积为0.86。结论: LINC01465可能是GA潜在的诊断及治疗靶点。

关键词: 痛风性关节炎, LINC01465, 机器学习, 信号通路

Abstract:

Objective To explore the potential pathogenesis-related long non-coding RNA (lncRNA) in gouty arthritis (GA) and the correlation with inflammatory factors. Methods GA microarray data were obtained from the Gene Expression Omnibus(GEO) database, and key lncRNA was identified and intersected by multiple machine learning methods. mRNAs co-expressed with lncRNAs were performed GO enrichment analysis. Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis was accomplished. The expression of key lncRNAs in GA patients was verified using quantitative real-time polymerase chain reaction(qRT-PCR) and the correlation between lncRNA and inflammatory factor levels was analyzed. The diagnostic value of LINC01465 expression levels in GA patients was analyzed by receiver operator characteristic(ROC) curves. Results One key lncRNA(LINC01465) was identified. GO enrichment analysis showed that the genes co-expressed with LINC01465 were enriched in RNA splicing, oxidative phosphorylation, reduced nicotinamide adenine dinucleotide (NADH ) dehydrogenase activity and other functions. KEGG signaling pathway analysis presented that it was mainly enriched in metabolic and inflammatory pathways such as nicotinate and nicotinamide metabolism, phosphoinositide 3-kinase(PI3K)-Akt, tumor necrosis factor signaling pathway. The qRT-PCR results exhibited that LINC01465 expression was upregulated in the patients with GA and was proportional to the expression of hematocrit, C-reactive protein and interleukin-6. The area under the receiver operator characteristic curve(AUC) was 0.86. Conclusions LINC01465 could be a potential diagnostic and therapeutic target for GA.

Key words: Gouty arthritis, LINC01465, Machine learning, Signaling pathway

中图分类号:

R593.22

肖剑伟, 蔡旭, 黄新民, 洪易炜, 汪荣盛. LINC01465在痛风性关节炎中的表达及临床意义[J]. 内科理论与实践, 2023, 18(02): 92-98.

XIAO Jianwei, CAI Xu, HUANG Xinmin, HONG Yiwei, WANG Rongsheng. Expression of LINC01465 in gouty arthritis and its clinical significances[J]. Journal of Internal Medicine Concepts & Practice, 2023, 18(02): 92-98.

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