Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery.
adipose‐deposition
lipidomics
liposuction
lymphedema
metabolomics
transcriptomics
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
revised:
11
09
2024
received:
07
03
2024
accepted:
24
09
2024
medline:
12
10
2024
pubmed:
12
10
2024
entrez:
12
10
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 39394863
doi: 10.1096/fj.202400498RR
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70097Subventions
Organisme : Fondation Leducq (Leducq Foundation)
ID : 11CVD03
Organisme : Novo Nordisk Fonden (NNF)
ID : NNF16OC0023554
Organisme : Cancerfonden (Swedish Cancer Society)
ID : CAN 2016/639
Organisme : Cancerfonden (Swedish Cancer Society)
ID : CAN 2013/505
Organisme : Skåne County Council's Research and Development Foundation (Skane County Council's Research and Development Foundation)
ID : REGSKANE-454091
Organisme : Skåne County Council's Research and Development Foundation (Skane County Council's Research and Development Foundation)
ID : REGSKANE-626131
Organisme : Skåne County Council's Research and Development Foundation (Skane County Council's Research and Development Foundation)
ID : REGSKANE-816751
Organisme : Skåne County Council's Research and Development Foundation (Skane County Council's Research and Development Foundation)
ID : Project 2020-0460
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)
ID : P300PB_164732
Organisme : Research Council of Finland (AKA)
ID : 330053
Organisme : Research Council of Finland (AKA)
ID : 297245
Organisme : WRI | Jenny ja Antti Wihurin Rahasto (Jenny JA Antti Wihurin Rahasto sr)
Organisme : Orion | Orionin Tutkimussäätiö (Orion Research Foundation)
Organisme : Sydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research)
Organisme : Maud Kuistilan Muistosäätiö (Maud Kuistila Foundation)
Organisme : University of Helsinki
Organisme : Sigrid Juséliuksen Säätiö (Sigrid Jusélius Stiftelse)
Informations de copyright
© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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