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Series GSE226898 Query DataSets for GSE226898
Status Public on Mar 11, 2024
Title Integrative study of mitochondrial dysfunction in murine skeletal muscle during pancreatic cancer cachexia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Pancreatic Ductal AdenoCarcinoma (PDAC), the most common pancreatic cancer, is a deadly cancer since it is often diagnosed late and resistant to current therapies. A large proportion of PDAC patients are affected by tumor-induced cachexia. This cachexia, characterized by a loss of muscle mass and strength (sarcopenia), contributes to patient frailty and poor therapeutic response. We have shown that mitochondrial metabolism is reprogrammed in PDAC tumors and constitutes a vulnerability, opening new therapeutic avenues. The objective of this work was to study the molecular mechanisms underlying mitochondrial remodeling in PDAC cachectic skeletal muscle. Our study focused on the gastrocnemius muscle of genetically-engineered mice spontaneously developing an autochthonous pancreatic tumor and cachexia (KIC GEMM). We compared KIC mice developing a pancreatic tumor in 9-11 weeks to control littermates. We performed an integrative study combining in vivo functional analyses by non-invasive Magnetic Resonance, and ex-vivo histology, Seahorse, RNA-sequencing, and proteomic mass spectrometry and Western blotting analyses. KIC cachectic PDAC mice exhibit severe sarcopenia with loss of muscle mass and strength associated with reduced muscle fiber’s size and induction of protein degradation processes. Mitochondrial alterations in skeletal muscle play a central role in PDAC-induced cachexia. Muscle atrophy is associated with strong mitochondrial metabolic defects that are not limited to carbohydrates and protein metabolism, but concern also lipids, ROS and nucleic acids. Our data provide a framework to guide towards the most relevant molecular markers that would be affected early in tumor development and could be targeted in the clinic to limit PDAC-induced cachexia at early stages of the pathology.
 
Overall design Comparative gene expression of gastrocnemius skeletal muscle of pancreatic cancer carrying mice versus healthy control using bulk RNA sequencing
 
Contributor(s) Marchiano F, Cicquel T, Carrier A, Habermann B
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Submission date Mar 08, 2023
Last update date Mar 11, 2024
Contact name Bianca Hermine Habermann
E-mail(s) bianca.habermann@univ-amu.fr
Organization name IBDM UMR7288
Lab Computational Biology
Street address Avenue de Luminy 163
City Marseille
ZIP/Postal code 13009
Country France
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7086615 Cancer KIC Male 9-11 weeks replicate 1 [Cancer-KIC-Male-7]
GSM7086616 Cancer KIC Male 9-11 weeks replicate 2 [Cancer-KIC-Male-8]
GSM7086617 Cancer KIC Male 9-11 weeks replicate 3 [Cancer-KIC-Male-9]
Relations
BioProject PRJNA942206

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE226898_KIC_vs_control_DEG-results.txt.gz 2.5 Mb (ftp)(http) TXT
GSE226898_KIC_vs_control_normalized_counts.csv.gz 1.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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