Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Profiling of Matched Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways

Ashok Narasimhan
,
Xiaoling Zhong
,
Ernie Au
,
Eugene P. Ceppa
,
Atilla Nakeeb
,
Michael G. House
,
Nicholas J. Zyromski
,
C. Max Schmidt
,
Katharyn N.H. Schloss
,
Daniel E.I. Schloss
,
Yunlong Liu
ORCID logo ,
Guanglong Jiang
,
Bradley A. Hancock
,
Milan Radovich
,
Joshua K. Kays
,
Safi Shahda
,
Marion E. Couch
,
Leonidas G. Koniaris
,
Teresa A. Zimmers
* ORCID logo
Version 1 : Received: 25 March 2021 / Approved: 26 March 2021 / Online: 26 March 2021 (11:24:10 CET)

A peer-reviewed article of this Preprint also exists.

Narasimhan, A.; Zhong, X.; Au, E.P.; Ceppa, E.P.; Nakeeb, A.; House, M.G.; Zyromski, N.J.; Schmidt, C.M.; Schloss, K.N.H.; Schloss, D.E.I.; Liu, Y.; Jiang, G.; Hancock, B.A.; Radovich, M.; Kays, J.K.; Shahda, S.; Couch, M.E.; Koniaris, L.G.; Zimmers, T.A. Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways. Cancers 2021, 13, 1975. Narasimhan, A.; Zhong, X.; Au, E.P.; Ceppa, E.P.; Nakeeb, A.; House, M.G.; Zyromski, N.J.; Schmidt, C.M.; Schloss, K.N.H.; Schloss, D.E.I.; Liu, Y.; Jiang, G.; Hancock, B.A.; Radovich, M.; Kays, J.K.; Shahda, S.; Couch, M.E.; Koniaris, L.G.; Zimmers, T.A. Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways. Cancers 2021, 13, 1975.

Abstract

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Keywords

Pancreatic cancer; RNAseq; Humans; Weight loss; Prognosis; Rectus Abdominis; Carcinoma, Pancreatic Ductal; Adipose Tissue; Pancreatic Carcinoma; Pancreatic Neoplasms; Subcutaneous Fat; High-Throughput Nucleotide Sequencing; Body Composition; Muscles; Cachexia; Muscular Atrophy; Gene Expression

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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