ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2024
Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed.
- A perforator-based adipocutaneous skin paddle derived from free muscle flap reconstruction as a hypothesis-generating human tissue model of early localized lymphatic insufficiency.Scientific reports · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Lymphedema: current treatment strategies and future directions in tissue engineering.Frontiers in medicine · 2026Review
- From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.Frontiers in immunology · 2026Review
- Liubao tea as a functional fermented food: multi-omics insights into its modulation of lymphatic endothelial cell metabolism.Frontiers in nutrition · 2026Article
- Therapeutic targeting of local metabolic dysfunction in secondary lymphedema: mechanisms and opportunities.Frontiers in physiology · 2026Review
- lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema.Science advances · 2025Article
- Analysis of Risk Factors of Lymphedema After Surgical Treatment in Cervical Cancer: A Case-Control Retrospective Study.International journal of general medicine · 2025Article
- Advances in etiology, pathophysiology, diagnosis, and management of lymphedema: a comprehensive review.Frontiers in medicine · 2025Review
- Identification of novel hub genes and pathways predictive of fibrosis progression in cancer-related lymphedema through integrated multi-omics.Frontiers in immunology · 2025Article
- Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
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Abstract
Secondary lymphedema (LE) following breast cancer-related surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity-induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell-cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched-chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non-LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer-related surgery. We also show distinct differences in transcriptomic signatures between LE-induced adipose tissue and obesity-induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non-LE arm.
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