Department of rheumatology and immunology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
School of Medicine, Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Guangzhou Key Laboratory of Germ-free Animals and Microbiota Application, Jinan University, Guangzhou, China.
PLoS One. 2024 May 16;19(5):e0296034. doi: 10.1371/journal.pone.0296034. eCollection 2024.
Dermatomyositis (DM) is prone to nasopharyngeal carcinoma (NPC), but the mechanism is unclear. This study aimed to explore the potential pathogenesis of DM and NPC.
The datasets GSE46239, GSE142807, GSE12452, and GSE53819 were downloaded from the GEO dataset. The disease co-expression module was obtained by R-package WGCNA. We built PPI networks for the key modules. ClueGO was used to analyze functional enrichment for the key modules. DEG analysis was performed with the R-package "limma". R-package "pROC" was applied to assess the diagnostic performance of hub genes. MiRNA-mRNA networks were constructed using MiRTarBase and miRWalk databases.
The key modules that positively correlated with NPC and DM were found. Its intersecting genes were enriched in the negative regulation of viral gene replication pathway. Similarly, overlapping down-regulated DEGs in DM and NPC were also enriched in negatively regulated viral gene replication. Finally, we identified 10 hub genes that primarily regulate viral biological processes and type I interferon responses. Four key genes (GBP1, IFIH1, IFIT3, BST2) showed strong diagnostic performance, with AUC>0.8. In both DM and NPC, the expression of key genes was correlated with macrophage infiltration level. Based on hub genes' miRNA-mRNA network, hsa-miR-146a plays a vital role in DM-associated NPC.
Our research discovered pivot genes between DM and NPC. Viral gene replication and response to type I interferon may be the crucial bridge between DM and NPC. By regulating hub genes, MiR-146a will provide new strategies for diagnosis and treatment in DM complicated by NPC patients. For individuals with persistent viral replication in DM, screening for nasopharyngeal cancer is necessary.
皮肌炎(DM)易并发鼻咽癌(NPC),但其机制尚不清楚。本研究旨在探讨 DM 和 NPC 的潜在发病机制。
从 GEO 数据库中下载数据集 GSE46239、GSE142807、GSE12452 和 GSE53819。使用 R 包 WGCNA 获取疾病共表达模块。我们为关键模块构建了 PPI 网络。使用 ClueGO 对关键模块进行功能富集分析。使用 R 包“limma”进行 DEG 分析。使用 R 包“pROC”评估关键基因的诊断性能。使用 MiRTarBase 和 miRWalk 数据库构建 miRNA-mRNA 网络。
发现与 NPC 和 DM 呈正相关的关键模块。其相交基因富集于病毒基因复制途径的负调控。同样,DM 和 NPC 中重叠下调的 DEGs 也富集于负调控病毒基因复制。最后,我们确定了 10 个主要调节病毒生物过程和 I 型干扰素反应的关键基因。四个关键基因(GBP1、IFIH1、IFIT3、BST2)具有较强的诊断性能,AUC>0.8。在 DM 和 NPC 中,关键基因的表达与巨噬细胞浸润水平相关。基于 hub 基因的 miRNA-mRNA 网络,hsa-miR-146a 在 DM 相关 NPC 中发挥重要作用。
我们的研究发现了 DM 和 NPC 之间的枢纽基因。病毒基因复制和对 I 型干扰素的反应可能是 DM 和 NPC 之间的关键桥梁。通过调节枢纽基因,miR-146a 将为 DM 并发 NPC 患者的诊断和治疗提供新策略。对于 DM 中持续病毒复制的个体,有必要进行鼻咽癌筛查。