Yan Tao, Zhu Shijie, Shi Yu, Xie Changming, Zhu Miao, Zhang Yangyang, Wang Chunsheng, Guo Changfa
Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Front Cardiovasc Med. 2021 Sep 3;8:713983. doi: 10.3389/fcvm.2021.713983. eCollection 2021.
Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer. Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA). was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of increased in diverse cancer types. Survival analysis suggested prognostic significance of expression levels in various cancer types. Immune correlation analysis indicated that expression levels were associated with tumor immune infiltration in most cancer types. might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway. was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. might play crucial roles in AF and cancer, and targeted therapy for might reduce the incidence of AF in cancer patients.
心房颤动（AF）是全球最常见的快速性心律失常。癌症是全球主要死因之一。最近一项研究表明，癌症与AF发病率增加有关。在本研究中，我们旨在探索AF与癌症之间可能的机制和潜在的共同治疗靶点。利用蛋白质组学分析鉴定AF与窦性心律之间差异表达的蛋白质。应用加权基因共表达网络分析将蛋白质聚类到不同模块，并研究模块与AF之间的关联。通过InnateDB数据库选择枢纽免疫相关基因，并使用qRT-PCR进行验证。从癌症基因组图谱（TCGA）获得33种不同癌症类型的RNA测序和临床数据。利用Cox回归分析和Kaplan-Meier生存分析计算表达与预后之间的相关性。使用Spearman等级相关检验评估与免疫浸润和DNA甲基化之间的关联。通过基因本体论和基因集富集分析（GSEA）进行富集分析。被鉴定为AF与窦性心律之间的枢纽免疫相关基因。在多种癌症类型中表达水平升高。生存分析表明表达水平在各种癌症类型中具有预后意义。免疫相关性分析表明，在大多数癌症类型中，表达水平与肿瘤免疫浸润相关。可能通过肿瘤负荷和微卫星不稳定性影响免疫治疗的疗效。GSEA结果表明，高表达组主要富集在过氧化物酶体、胆汁酸生物合成和p53途径中。被鉴定为AF中一个从未被报道过的枢纽免疫相关基因。泛癌分析表明其作为多种癌症类型中新型临床预后标志物和治疗靶点的潜力。可能在AF和癌症中起关键作用，针对的靶向治疗可能降低癌症患者AF的发病率。
