ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1625972
This article is part of the Research TopicImmunological Aspects of Fibrosis Pathogenesis: Novel Mechanisms and Therapeutic StrategiesView all 24 articles
Identification of Novel Hub Genes and Pathways Predictive of Fibrosis Progression in Cancer-Related Lymphedema Through Integrated Multi-Omics
Provisionally accepted
- Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Cancer-related lymphedema (CRL), a chronic swelling condition often arising after cancer therapy, is characterized by progressive fibrosis of affected tissues, particularly within adipose tissue, leading to late-stage irreversible swelling and dysfunction, ultimately impairing patients' quality of life. However, the contributions and mechanisms of adipose tissue fibrosis in CRL have been largely overlooked and remain poorly understood. In this study, we addressed this critical knowledge gap by conducting, to our knowledge, the first comprehensive multi-omics analysis of fibrotic adipose tissue in CRL. We integrated multi-omics datasets in an innovative approach to systematically identify novel hub genes and pathways predictive of fibrosis progression. This integrative strategy pinpointed a network of dysregulated genes and signaling pathways, highlighting extracellular matrix (ECM) remodeling as a central pathological process in CRL fibrogenesis. Among these molecular changes, Asporin (ASPN), an extracellular matrix protein, emerged as a critical hub gene. Notably, ASPN was significantly upregulated in fibrotic adipose tissue of CRL patients, and its expression correlated strongly with disease duration and fibrosis severity. Furthermore, single-cell transcriptomic analysis revealed that ASPN is predominantly expressed by adipose-derived mesenchymal stem cells (ADSCs) within lymphedematous tissue, implicating these cells as key mediators of ASPN-related fibrosis. Importantly, inflammatory signaling pathways, including TNF, IFN, IL-1, CCL, and MIF, suggest that inflammatory cues may drive or amplify fibrotic remodeling in CRL. These findings underscore the pivotal involvement of adipose tissue fibrosis in CRL pathophysiology and spotlight ASPN as a promising predictive biomarker of fibrosis progression.
Keywords: cancer-related lymphedema, Fibrosis, Bioinformatics analysis, inflamation, ASPORIN
Received: 09 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Chen, Chen, Wang, Deng, Zhou, Wang, Xiao and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chengliang Deng, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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