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皮肌炎与癌症之间潜在联系的分析

英文原题:Analysis of the Potential Link Between Dermatomyositis and Cancer.

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Analysis of the Potential Link Between Dermatomyositis and Cancer.

PubMed 2024/12/03(内容时间) J Inflamm Res Q2 · IF 4.6(JCR 2025)

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研究概要

研究结果表明,MIF、C1QA 和 CDKN1A 在 DM 患者中差异表达,其中 MIF 在合并癌症的 DM 患者中表现出显著改变。MIF 可能作为多种癌症的重要预后生物标志物和治疗靶点,通过调节 CD4+ Th1 细胞、NKT 细胞和 MDSCs,在 DM 与癌症的关联中发挥关键作用。

研究思路结论见上方概要

皮肌炎(DM)是一种炎症性肌肉疾病,会增加癌症风险,尽管其确切联系尚未完全明确。本研究旨在探讨DM与癌症关联的机制,并确定潜在的治疗靶点。

我们对GSE128470数据集进行了差异基因表达分析,并采用WGCNA来识别与DM相关的关键基因。通过LASSO和SVM-RFE方法确定了核心基因。这些基因的表达水平和诊断相关性通过GSE1551数据集得到验证。分析了免疫细胞浸润与核心基因的关系,并利用RT‒qPCR评估了关键基因在多种癌症中的表达。

共鉴定出差异表达基因(DEGs),主要涉及固有免疫、细胞因子反应和自身免疫性疾病。在WGCNA中,共鉴定出399个与DM相关的显著基因,核心基因包括MIF、C1QA和CDKN1A。免疫浸润分析显示DM患者中存在多种免疫细胞群体,且核心基因与这些免疫细胞之间具有显著相关性。MIF水平在多种肿瘤中显著升高,并与特定癌症的预后相关。此外,MIF与大多数免疫细胞呈负相关,但与CD4+ Th1细胞、NKT细胞和MDSCs呈正相关。免疫调节元件、TMB和MSI等因素表明MIF可能影响免疫治疗结局。RT‒qPCR证实了MIF mRNA表达升高。

展开英文摘要原文

Dermatomyositis (DM) is an inflammatory muscle disease that increases the risk of cancer, although the precise connection is not fully understood. The aim of this study was to investigate the mechanisms linking DM to cancer and identify potential therapeutic targets.

We conducted differential gene expression analysis on the GSE128470 dataset and employed WGCNA to pinpoint key genes related to DM. Central genes were identified with the LASSO and SVM-RFE methods. The expression levels and diagnostic relevance of these genes were confirmed via the GSE1551 dataset. Immune cell infiltration was analyzed in relation to central genes, and RT‒qPCR was utilized to evaluate the expression of key genes across various cancers.

In total, differentially expressed genes (DEGs), involved mainly in innate immunity, cytokine responses, and autoimmune diseases, were identified. In the WGCNA, 399 significant genes related to DM were identified, with central genes including MIF, C1QA, and CDKN1A. Immune infiltration analysis revealed diverse immune cell populations in DM patients, with significant correlations between central genes and these immune cells. MIF levels were notably elevated in various tumors and correlated with the prognosis of specific cancers. Furthermore, MIF was negatively associated with most immune cells but positively correlated with CD4+ Th1 cells, NKT cells, and MDSCs. Factors such as immune regulatory elements, TMB, and MSI indicated that MIF may affect immunotherapy outcomes. The increased expression of MIF mRNA was confirmed via RT‒qPCR.

The findings demonstrate that MIF, C1QA, and CDKN1A are differentially expressed in DM patients, with MIF showing significant alterations in DM patients with cancer. MIF may serve as a crucial prognostic biomarker and therapeutic target for various cancers, playing a pivotal role in linking DM to cancer through the modulation of CD4+ Th1 cells, NKT cells, and MDSCs.

论文信息

作者
Guo J、Lei T、Yu X、Wang P、Xie H、Jian G、Zhang Q、Qing Y
单位
Research Center of Hyperuricemia and Gout, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People's Republic of China.China
期刊
Journal of inflammation research2024
原文标识
PubMed 39649426 · DOI 10.2147/JIR.S480744