Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways
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 ident...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-04-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/13/8/1975 |
id |
doaj-5197e193189f4c75a8d297f130f6e060 |
---|---|
record_format |
Article |
spelling |
doaj-5197e193189f4c75a8d297f130f6e0602021-04-20T23:01:46ZengMDPI AGCancers2072-66942021-04-01131975197510.3390/cancers13081975Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent PathwaysAshok Narasimhan0Xiaoling Zhong1Ernie P. Au2Eugene P. Ceppa3Atilla Nakeeb4Michael G. House5Nicholas J. Zyromski6C. Max Schmidt7Katheryn N. H. Schloss8Daniel E. I. Schloss9Yunlong Liu10Guanglong Jiang11Bradley A. Hancock12Milan Radovich13Joshua K. Kays14Safi Shahda15Marion E. Couch16Leonidas G. Koniaris17Teresa A. Zimmers18Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USAIUPUI Center for Cachexia Research Innovation and Therapy, Indianapolis, IN 46202, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USAIUPUI Center for Cachexia Research Innovation and Therapy, Indianapolis, IN 46202, USAIUPUI Center for Cachexia Research Innovation and Therapy, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USAThe 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 (<i>n</i> = 11) and patients with PDAC (<i>n</i> = 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.https://www.mdpi.com/2072-6694/13/8/1975pancreatic cancerpancreatic ductal adenocarcinomagene expressionRNAseqadiposeskeletal muscle |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ashok Narasimhan Xiaoling Zhong Ernie P. Au Eugene P. Ceppa Atilla Nakeeb Michael G. House Nicholas J. Zyromski C. Max Schmidt Katheryn N. H. Schloss Daniel E. I. Schloss Yunlong Liu Guanglong Jiang Bradley A. Hancock Milan Radovich Joshua K. Kays Safi Shahda Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers |
spellingShingle |
Ashok Narasimhan Xiaoling Zhong Ernie P. Au Eugene P. Ceppa Atilla Nakeeb Michael G. House Nicholas J. Zyromski C. Max Schmidt Katheryn N. H. Schloss Daniel E. I. Schloss Yunlong Liu Guanglong Jiang Bradley A. Hancock Milan Radovich Joshua K. Kays Safi Shahda Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways Cancers pancreatic cancer pancreatic ductal adenocarcinoma gene expression RNAseq adipose skeletal muscle |
author_facet |
Ashok Narasimhan Xiaoling Zhong Ernie P. Au Eugene P. Ceppa Atilla Nakeeb Michael G. House Nicholas J. Zyromski C. Max Schmidt Katheryn N. H. Schloss Daniel E. I. Schloss Yunlong Liu Guanglong Jiang Bradley A. Hancock Milan Radovich Joshua K. Kays Safi Shahda Marion E. Couch Leonidas G. Koniaris Teresa A. Zimmers |
author_sort |
Ashok Narasimhan |
title |
Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways |
title_short |
Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways |
title_full |
Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways |
title_fullStr |
Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways |
title_full_unstemmed |
Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways |
title_sort |
profiling of adipose and skeletal muscle in human pancreatic cancer cachexia reveals distinct gene profiles with convergent pathways |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-04-01 |
description |
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 (<i>n</i> = 11) and patients with PDAC (<i>n</i> = 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. |
topic |
pancreatic cancer pancreatic ductal adenocarcinoma gene expression RNAseq adipose skeletal muscle |
url |
https://www.mdpi.com/2072-6694/13/8/1975 |
work_keys_str_mv |
AT ashoknarasimhan profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT xiaolingzhong profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT erniepau profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT eugenepceppa profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT atillanakeeb profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT michaelghouse profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT nicholasjzyromski profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT cmaxschmidt profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT katherynnhschloss profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT danieleischloss profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT yunlongliu profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT guanglongjiang profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT bradleyahancock profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT milanradovich profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT joshuakkays profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT safishahda profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT marionecouch profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT leonidasgkoniaris profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways AT teresaazimmers profilingofadiposeandskeletalmuscleinhumanpancreaticcancercachexiarevealsdistinctgeneprofileswithconvergentpathways |
_version_ |
1721517250926608384 |