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鉴定与心力衰竭中 CD8T 细胞相关的枢纽模块和治疗靶点及其泛癌分析。

Identification of hub modules and therapeutic targets associated with CD8T-cells in HF and their pan-cancer analysis.

机构信息

School of Life Science and Biochemistry, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, Liaoning Province, China.

State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Wenhua Road 83, Shenyang, 110016, Liaoning Province, China.

出版信息

Sci Rep. 2024 Aug 13;14(1):18823. doi: 10.1038/s41598-024-68504-6.

Abstract

Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a deadly disease worldwide. The relationship between HF and cancer remains poorly understood. The Gene Expression Omnibus database was used to download the RNA sequencing data of 356 patients with hypertrophic cardiomyopathy-induced HF and non-HF. A co-expression network was established through the weighted correlation network analysis (WGCNA) to identify hub genes of HF and cancer. Cox risk analysis was performed to predict the prognostic risks of HF hub genes in pan-cancer. HF was linked to immune response pathway by the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A positive correlation was observed between the expression levels of 4 hub genes and the infiltration of CD8T-cells in pan-cancer. 4 hub genes were identified as beneficial prognostic factors in several cancers. Western blotting and real-time polymerase chain reaction validated the high expression of GZMM, NKG7, and ZAP70 in both mice and patients with HF compared to control groups. Our study highlights the shared immune pathogenesis of HF and cancer and provides valuable insights for developing novel therapeutic strategies, offering new opportunities for improving the management and treatment outcomes of both HF and cancer.

摘要

心力衰竭(HF)是多种心血管疾病的终末期病症。癌症是全球范围内的致命疾病。HF 和癌症之间的关系仍未被充分理解。本研究使用基因表达综合数据库(Gene Expression Omnibus database)下载了 356 例肥厚型心肌病诱导的 HF 和非 HF 患者的 RNA 测序数据。通过加权相关网络分析(weighted correlation network analysis,WGCNA)建立共表达网络,以识别 HF 和癌症的枢纽基因。通过 Cox 风险分析预测泛癌中 HF 枢纽基因的预后风险。通过基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,HF 与免疫反应途径相关联。在泛癌中观察到 4 个枢纽基因的表达水平与 CD8T 细胞浸润呈正相关。4 个枢纽基因在几种癌症中被确定为有益的预后因素。Western blot 和实时聚合酶链反应验证了 HF 小鼠和患者中 GZMM、NKG7 和 ZAP70 的高表达,与对照组相比。本研究强调了 HF 和癌症的共同免疫发病机制,并为开发新的治疗策略提供了有价值的见解,为改善 HF 和癌症的管理和治疗结果提供了新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f2/11322555/6b13bd8fc5c6/41598_2024_68504_Fig1_HTML.jpg

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