| Title: |
Multi-omics characterization of lymphedema-induced adipose tissue resulting from breast cancer-related surgery |
| Authors: |
Karaman, Sinem; Lehti, Satu; Zhang, Cheng; Taskinen, Marja-Riitta; Käkelä, Reijo; Mardinoglu, Adil; Brorson, Håkan; Alitalo, Kari; Kivelä, Riikka |
| Contributors: |
INDIVIDRUG - Individualized Drug Therapy; Organotypic Vasculature Lab; Medicum; CAN-PRO - Translational Cancer Medicine Program; University of Helsinki; Faculty of Medicine; Clinicum; Marja-Riitta Taskinen Research Group; Research Programs Unit; CAMM - Research Program for Clinical and Molecular Metabolism; Molecular and Integrative Biosciences Research Programme; Functional Lipidomics Group; Department of Biochemistry and Developmental Biology; Helsinki Institute of Life Science HiLIFE; HUSLAB; Kari Alitalo / Principal Investigator; STEMM - Stem Cells and Metabolism Research Program; Kivelä Lab; HUS Radiology and Pathology |
| Publisher Information: |
John Wiley & Sons Ltd. |
| Publication Year: |
2024 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
adipose-deposition; lipidomics; liposuction; lymphedema; metabolomics; transcriptomics; Biomedicine |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
We gratefully acknowledge Dr. Bushra Shaida for the preparation of adipose tissue samples (Lund University); Mari Jokinen for RNA isolation, qPCR, and metabolomics sample preparations (Wihuri Research Institute); and Madeleine H. Lackman for help with circos plots (University of Helsinki). Bulk RNA isolation and sequencing were performed at the BEA Core Facility (Karolinska Institute). Metabolomics analyses were carried out at the Biocenter Finland and HiLIFE-supported Metabolomics Unit (Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki). This work was funded by the Leducq Foundation Transatlantic Network of Excellence Lymph Vessels in Obesity and Cardiovascular Disease (grant 11CVD03 to K.A.), Jenni and Antti Wihuri Foundation, and the Novo Nordisk Foundation (NNF16OC0023554). S.K. was supported by the Swiss National Science Foundation (Advanced Postdoc. Mobility grant number: P300PB_164732), Orion Research Foundation, Finnish Foundation for Cardiovascular Research, Maud Kuistila Memorial Foundation, Academy of Finland (330053), the Sigrid Juselius Foundation and University of Helsinki. R. Kivel\u00E4. was supported by the Academy of Finland (297245), the Sigrid Jus\u00E9lius Foundation, and the Finnish Foundation for Cardiovascular Research. H.B. was funded by the Swedish Cancer Society, Stockholm (CAN 2016/639, CAN 2013/505) and Sk\u00E5ne County Council's Research, and Development Foundation (REGSKANE-454091, REGSKANE-626131, REGSKANE-816751, Project 2020-0460). We gratefully acknowledge Dr. Bushra Shaida for the preparation of adipose tissue samples (Lund University); Mari Jokinen for RNA isolation, qPCR, and metabolomics sample preparations (Wihuri Research Institute); and Madeleine H. Lackman for help with circos plots (University of Helsinki). Bulk RNA isolation and sequencing were performed at the BEA Core Facility (Karolinska Institute). Metabolomics analyses were carried out at the Biocenter Finland and HiLIFE\u2010supported Metabolomics Unit (Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki). This work was funded by the Leducq Foundation Transatlantic Network of Excellence Lymph Vessels in Obesity and Cardiovascular Disease (grant 11CVD03 to K.A.), Jenni and Antti Wihuri Foundation, and the Novo Nordisk Foundation (NNF16OC0023554). S.K. was supported by the Swiss National Science Foundation (Advanced Postdoc. Mobility grant number: P300PB_164732), Orion Research Foundation, Finnish Foundation for Cardiovascular Research, Maud Kuistila Memorial Foundation, Academy of Finland (330053), the Sigrid Juselius Foundation and University of Helsinki. R. Kivel\u00E4. was supported by the Academy of Finland (297245), the Sigrid Jus\u00E9lius Foundation, and the Finnish Foundation for Cardiovascular Research. H.B. was funded by the Swedish Cancer Society, Stockholm (CAN 2016/639, CAN 2013/505) and Sk\u00E5ne County Council's Research, and Development Foundation (REGSKANE\u2010454091, REGSKANE\u2010626131, REGSKANE\u2010816751, Project 2020\u20100460).; https://hdl.handle.net/10138/587281; 85206123255; 001330093000001 |
| Availability: |
https://hdl.handle.net/10138/587281 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.2BD82196 |
| Database: |
BASE |