鉴定与冠状动脉疾病中 CD8+ T 细胞相关的生物标志物及其泛癌症分析。
Identification of Biomarkers Associated With CD8+ T Cells in Coronary Artery Disease and Their Pan-Cancer Analysis.
机构信息
Department of Cardiology, the Affiliated Cardiovascular Hospital of Kunming Medical University (Fuwai Yunnan Cardiovascular Hospital), Kunming, China.
Department of Orthopedic and Trauma Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, China.
出版信息
Front Immunol. 2022 Jun 21;13:876616. doi: 10.3389/fimmu.2022.876616. eCollection 2022.
PURPOSE
To identify biomarkers associated with CD8+ T cells in coronary artery disease (CAD) and initially explore their potential role in the tumor immune microenvironment.
MATERIALS AND METHODS
CAD-related datasets GSE12288, GSE34198, and GSE66360, were downloaded from the GEO database. First, GSVA was performed based on the GSE12288 dataset. Then WGCNA analysis was performed to identify the most relevant module and candidate hub gene for CD8+ T cells, followed by GO and KEGG analysis of this module. Secondly, the relationship between candidate hub genes and CD8+ T cells was verified using GSE34198 and GSE66360, which led to the identification of hub genes. The relationship of hub genes with CD8+ T cells in cancer was analyzed using the TIMER database. Methylation analysis of hub genes was performed using the DiseaseMeth database. CAD, pan-cancer, pan-cell lines, and pan-normal tissues, correlations between hub genes. In addition, potential drugs and TFs associated with hub genes were predicted, and the ceRNA network was constructed. Finally, GSEA was performed separately for hub genes.
RESULTS
CAD was shown to be associated with immune response by GSVA analysis. WGCNA identified the blue module as most related to CD8+ T cells and identified nine candidate hub genes. The relevance of CAD to immunity was further confirmed by GO and KEGG analysis of the module. Two additional datasets validated and identified three hub genes (FBXO7, RAD23A, and MKRN1) that significantly correlated with CD8+ T cells. In addition, we found that hub genes were positively associated with CD8+ T cells in TGCT, THCA, and KICH cancers by our analysis. Moreover, the hub gene was differentially methylated. We also analyzed the correlation between hub genes in CAD, different cancers, different cell lines, and different normal tissues. The results of all the analyses showed a positive correlation between them. Finally, we successfully constructed hub gene-associated TF-gene and ceRNA networks and predicted 11 drugs associated with hub genes. GSEA suggests that hub genes are related to multiple immune response processes.
CONCLUSION
FBXO7, RAD23A, and MKRN1 are significantly associated with CD8+ T cells in CAD and multiple cancers and may act through immune responses in CAD and cancer.
目的
鉴定与冠状动脉疾病（CAD）中 CD8+T 细胞相关的生物标志物，并初步探索其在肿瘤免疫微环境中的潜在作用。
材料和方法
从 GEO 数据库中下载了 CAD 相关数据集 GSE12288、GSE34198 和 GSE66360。首先，基于 GSE12288 数据集进行 GSVA。然后进行 WGCNA 分析，以确定与 CD8+T 细胞最相关的模块和候选枢纽基因，随后对该模块进行 GO 和 KEGG 分析。其次，使用 GSE34198 和 GSE66360 验证候选枢纽基因与 CD8+T 细胞的关系，从而确定枢纽基因。使用 TIMER 数据库分析枢纽基因与癌症中 CD8+T 细胞的关系。使用 DiseaseMeth 数据库对枢纽基因进行甲基化分析。分析枢纽基因在 CAD、泛癌、泛细胞系和泛正常组织中的相关性。此外，预测与枢纽基因相关的潜在药物和 TFs，并构建 ceRNA 网络。最后，分别对枢纽基因进行 GSEA。
结果
通过 GSVA 分析表明 CAD 与免疫反应有关。WGCNA 确定蓝色模块与 CD8+T 细胞最相关，并确定了 9 个候选枢纽基因。通过对模块的 GO 和 KEGG 分析进一步证实了 CAD 与免疫的相关性。另外两个数据集验证并确定了三个与 CD8+T 细胞显著相关的枢纽基因（FBXO7、RAD23A 和 MKRN1）。此外，我们通过分析发现，枢纽基因在 TGCT、THCA 和 KICH 癌症中与 CD8+T 细胞呈正相关。此外，枢纽基因发生了差异甲基化。我们还分析了 CAD、不同癌症、不同细胞系和不同正常组织中枢纽基因的相关性。所有分析的结果都显示它们之间呈正相关。最后，我们成功构建了枢纽基因相关的 TF-基因和 ceRNA 网络，并预测了 11 种与枢纽基因相关的药物。GSEA 表明枢纽基因与多种免疫反应过程有关。
结论
FBXO7、RAD23A 和 MKRN1 与 CAD 和多种癌症中的 CD8+T 细胞显著相关，可能通过 CAD 和癌症中的免疫反应发挥作用。
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