Multi-omics characterization of cachexia-related genes reveals prognostic signatures and immune landscape in breast cancer.

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical & Translational Oncology Pub Date : 2025-08-29 DOI:10.1007/s12094-025-04025-6

Siyu Wang, Hongxia Zhu, Wendi Zhan, Bo Hao, Zhuo Li, Taolan Zhang

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引用次数: 0

Abstract

Background: Cancer cachexia is a multifactorial syndrome affecting cancer prognosis and immune microenvironment. However, the roles of cachexia-related genes (CRGs) in breast cancer remain unclear.

Methods: We performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) on TCGA-BRCA data to identify key CRGs. A prognostic model was constructed using LASSO-Cox regression. Immune infiltration and treatment sensitivity were assessed, and single-cell RNA-seq analyses were conducted to explore gene function and cell-cell interactions.

Results: A total of 82 CRGs were identified, and an 11-gene prognostic model was constructed, showing high predictive accuracy across multiple cohorts. Based on this model, we created a new risk score (Cachexia-related Risk Score for Breast Cancer, CRSBC) to categorize patients into high and low-risk groups. Low-risk patients had a better prognosis and good immune infiltration with higher sensitivity to immunotherapy. Single-cell analysis revealed HCCS as a key gene enriched in epithelial cells (breast cancer cells) and involved in macrophages recruitment via the MIF signaling pathway.

Conclusions: This study reveals the prognostic and immunological significance of CRGs in breast cancer and highlights HCCS as a potential therapeutic target.

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恶病质相关基因的多组学特征揭示了乳腺癌的预后特征和免疫景观。

背景：癌症恶病质是影响肿瘤预后和免疫微环境的多因素综合征。然而，恶病质相关基因（CRGs）在乳腺癌中的作用尚不清楚。方法：对TCGA-BRCA数据进行差异表达分析和加权基因共表达网络分析（WGCNA），鉴定关键的CRGs。采用LASSO-Cox回归建立预后模型。评估免疫浸润和治疗敏感性，并进行单细胞RNA-seq分析以探索基因功能和细胞间相互作用。结果：共鉴定出82个crg，并构建了一个11个基因的预后模型，在多个队列中具有较高的预测准确性。基于该模型，我们创建了一个新的风险评分（恶病质相关风险评分for Breast Cancer， CRSBC），将患者分为高危组和低危组。低危患者预后较好，免疫浸润良好，对免疫治疗的敏感性较高。单细胞分析显示，HCCS是上皮细胞（乳腺癌细胞）中富集的关键基因，并通过MIF信号通路参与巨噬细胞募集。结论：本研究揭示了CRGs在乳腺癌中的预后和免疫学意义，并强调了HCCS是一个潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.