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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\u2010induced LE in short\u2010 and long\u2010term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity\u2010induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer\u2010operated females with LE from the affected and non\u2010affected arms (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920 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\u2013cell 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\u2010induced and the obesity\u2010induced 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\u2010chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter\n                    <jats:italic>SLC6A15<\/jats:italic>\n                    . Lipidomics analyses did not show any significant differences between the LE and non\u2010LE 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\u2010related surgery. We also show distinct differences in transcriptomic signatures between LE\u2010induced adipose tissue and obesity\u2010induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non\u2010LE arm.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400498rr","type":"journal-article","created":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T05:20:41Z","timestamp":1728710441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Multi\u2010omics characterization of lymphedema\u2010induced adipose tissue resulting from breast cancer\u2010related surgery"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0719-1773","authenticated-orcid":false,"given":"Sinem","family":"Karaman","sequence":"first","affiliation":[{"name":"Wihuri Research Institute  Helsinki Finland"},{"name":"Translational Cancer Medicine Research Program Faculty of Medicine, 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