Fu Zhenyang, Lin Zongrong, Chen Sicheng, Xie Haomin, Wen Haolin, Huang Yuexun, Chen Jiyan
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincia People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China.
Med Oncol. 2025 Aug 4;42(9):406. doi: 10.1007/s12032-025-02933-9.
Cardiac cachexia linked to lung adenocarcinoma (LCACC) is a clinically important yet under-researched issue in cardio-oncology. LCACC is caused directly by the progression of the tumor, unlike cardiotoxicity induced by therapy. We proposed that LCACC myocardium exhibits unique transcriptomic and immunometabolic profiles.
To thoroughly analyze the molecular alterations in the myocardium associated with LCACC and pinpoint possible regulatory genes and therapeutic targets.
We conducted a comprehensive bioinformatics analysis using publicly accessible myocardial RNA-seq data (n = 4 + 4) from LCACC and control mice. The analyses comprised differential gene expression (DEG), immune deconvolution using xCell, gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) networks.
In LCACC, the myocardium exhibited metabolic reprogramming characterized by increased oxidative phosphorylation (OXPHOS) and protein synthesis pathways, while cell cycle and inflammatory signaling (such as NF-κB) were downregulated. The analysis of immune profiles indicated a rise in fibroblasts and megakaryocyte-erythroid progenitors, while conventional dendritic and memory B cells were reduced. Five central genes (CCL2, CDC20, MKI67, CX3CR1, CXCL1) were discovered, grouped within chemokine signaling and cell division pathways, and linked to actionable upstream transcription factors, miRNAs, and possible drugs.
This research offers the initial comprehensive map of transcriptomic and immunometabolic changes in LCACC. These results emphasize that LCACC involves active, regulated biological processes, indicating it is not just a passive result of cachexia, and they pave the way for further mechanistic and translational studies.
与肺腺癌相关的心脏恶病质（LCACC）是心脏肿瘤学中一个临床重要但研究不足的问题。与治疗引起的心脏毒性不同，LCACC是由肿瘤进展直接导致的。我们提出LCACC心肌表现出独特的转录组和免疫代谢特征。
全面分析与LCACC相关的心肌分子改变，确定可能的调控基因和治疗靶点。
我们使用来自LCACC和对照小鼠的公开可用心肌RNA测序数据（n = 4 + 4）进行了全面的生物信息学分析。分析包括差异基因表达（DEG）、使用xCell进行免疫反卷积、基因集富集分析（GSEA）、加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络。
在LCACC中，心肌表现出代谢重编程，其特征是氧化磷酸化（OXPHOS）和蛋白质合成途径增加，而细胞周期和炎症信号（如NF-κB）下调。免疫特征分析表明成纤维细胞和巨核细胞-红系祖细胞增加，而传统树突状细胞和记忆B细胞减少。发现了五个中心基因（CCL2、CDC20、MKI67、CX3CR1、CXCL1），它们归类于趋化因子信号传导和细胞分裂途径，并与可操作的上游转录因子、miRNA和可能的药物相关。
本研究提供了LCACC转录组和免疫代谢变化的初步综合图谱。这些结果强调LCACC涉及活跃的、受调控的生物学过程，表明它不仅仅是恶病质的被动结果，为进一步的机制和转化研究铺平了道路。
