中国麻风皮肤病杂志 ›› 2026, Vol. 42 ›› Issue (8): 553-560.doi: 10.12144/zgmfskin202608553

• 论著 • 上一篇    下一篇

PD-1抑制剂免疫相关皮肤不良反应患者外周血miRNA表达差异及生物信息学分析

黄云帆*,李琳彤*,刘玉洋,尤婉纯,覃瑶,郑跃   

  1. 南方医科大学南方医院皮肤科，广东广州，510515 *共同第一作者
  • 出版日期:2026-08-15 发布日期:2026-08-03

Differential expression and bioinformatics analysis of peripheral blood miRNAs in patients with PD-1 inhibitor-induced cutaneous immune-related adverse events

HUANG Yunfan*, LI Lintong*, LIU Yuyang, YOU Wanchun, QIN Yao, ZHENG Yue   

  1. Department of Dermatology, Southern Medical University, Nanfang Hospital, Guangzhou 510515, China *Co-first authors
  • Online:2026-08-15 Published:2026-08-03

PDF (PC)

44

摘要： 目的：明确PD-1抑制剂诱发的免疫相关皮肤不良反应（cutaneous immune-related adverse events, cirAE）患者与未出现cirAE患者外周血微小RNA（miRNA）差异性表达情况及生物信息学特征。方法：收集就诊于南方医科大学南方医院的3例cirAE患者和1例未出现cirAE的肿瘤患者的外周血，使用转录组测序技术分析两组的差异miRNA表达谱，构建热图和火山图。利用RNAhybrid、miRanda和TargetScan数据库进行筛选，将数据库中共有的mRNA定义为该miRNA的靶基因，利用基因本体（GO）和京都基因与基因组百科全书（KEGG）对靶基因进行鉴定和功能富集分析。通过实时定量聚合酶链反应（RT-qPCR）验证miRNA的表达差异。 结果：将cirAE组的miRNA表达谱与对照组进行差异表达分析，共筛选出72个差异表达的miRNA，其中上调的有34个，下调的有38个。cirAE患者表达上调最显著的miRNA为miR-15a-5p（log2FC=7.71，FDR＜0.001）和 miR-10a（log2FC=6.67，FDR＜0.001）。GO分析表明，显著差异表达的miRNA靶基因主要参与细胞部分与细胞器部分、免疫系统过程、代谢过程、生物过程的调节、信号转导和结合活性等生物学过程；KEGG通路分析显示靶基因显著富集于PI3K-Akt、VEGF等信号通路及黏附连接等。RT-qPCR结果与测序结果相符。结论：本研究初步绘制PD-1抑制剂诱发cirAE患者外周血miRNA差异表达谱，鉴定出miR-15a-5p、miR-10a是关键非编码RNA，从表观遗传维度为PD-1抑制剂cirAE的早期预测、诊断及治疗靶点开发提供初步实验证据。

关键词: 免疫相关皮肤不良反应, PD-1抑制剂, 微小RNA, 转录组测序技术, 转录组学

Abstract: Objective: To explore the potential pathogenesis of PD-1 inhibitor-induced cutaneous immune-related adverse events (cirAEs) by analyzing differentially expressed miRNAs and conducting bioinformatics studies in the peripheral blood of patients with cirAEs induced by PD-1 inhibitors compared to those without cirAEs. Methods: Peripheral blood samples were collected from three patients with cirAEs and one patient without cirAEs at Southern Medical University, Nanfang Hospital. Transcriptome sequencing was used to analyze the differential miRNA expression profiles between the two groups, and heatmaps and volcano plots were constructed. Target mRNAs were screened using RNAhybrid, miRanda, and TargetScan databases. The common mRNAs identified across the databases were defined as target genes of the respective miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed for the identification and functional enrichment analysis of the target genes. The expression differences of miRNAs were verified using real-time quantitative polymerase chain reaction (RT-qPCR). Results: A comparison between the cirAE group and the control group revealed 72 differentially expressed miRNAs, including 34 upregulated and 38 downregulated miRNAs. The most significantly upregulated miRNAs in cirAE patients were miR-15a-5p (log2FC=7.71, FDR＜0.001) and miR-10a (log2FC=6.67, FDR＜0.001). GO analysis indicates that the significantly differentially expressed miRNA target genes are primarily involved in cellular component and organelle, immune system process, metabolic process, regulation of biological process, signaling, and binding, etc. KEGG pathway analysis reveals significant enrichment of target genes in pathways including PI3K-Akt, VEGF signaling pathways, adherens junction, etc. RT-qPCR results supported the sequencing data. Conclusion: There was a significant alteration in miRNA expression in the peripheral blood of cirAE patients. miR-15a-5p and miR-10a may regulate immune system processes and metabolic processes through the PI3K-Akt signaling pathway, participating in the occurrence of cirAEs.

Key words: cutaneous immune-related adverse events (cirAEs), PD-1 inhibitors, mircoRNA (miRNA), transcriptome sequencing, transcriptomics