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J Clin Endocrinol Metab. 2019 Nov 1;104(11):5225-5237. doi: 10.1210/jc.2019-00461.

Transcriptome Profiling of Adipose Tissue Reveals Depot-Specific Metabolic Alterations Among Patients with Colorectal Cancer.

Author information

1
Division of Translational Functional Cancer Genomics, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany.
2
Division of Translational Medical Oncology, National Center for Tumor Diseases Dresden and German Cancer Research Center, Dresden, Germany.
3
Division of Preventive Oncology, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany.
4
Huntsman Cancer Institute, Salt Lake City, Utah.
5
Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.
6
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
7
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
8
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
9
Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
10
Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
11
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
12
NCT Tissue Bank, National Center for Tumor Diseases and University Hospital Heidelberg, Heidelberg, Germany.
13
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
14
Institute of Pathology, University Medicine Mainz, Mainz, Germany.
15
Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.
16
Center for Personalized Oncology, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
17
DKTK, Dresden, Germany.
18
Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany.

Abstract

CONTEXT:

Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking.

OBJECTIVE:

We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression.

DESIGN:

Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT.

RESULTS:

VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism-related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression.

CONCLUSIONS:

This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass-associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.

PMID:
31225875
PMCID:
PMC6763280
[Available on 2020-06-21]
DOI:
10.1210/jc.2019-00461

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