The muscle and adipose transcriptome data from patients with PDAC cachexia
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ABSTRACT:
PROVIDER: PRJNA553243 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9655380.fastq.gz | Fastqsanger.gz | |||
| SRR9655390.fastq.gz | Fastqsanger.gz | |||
| SRR9655400.fastq.gz | Fastqsanger.gz | |||
| SRR9655410.fastq.gz | Fastqsanger.gz | |||
| SRR9655420.fastq.gz | Fastqsanger.gz |
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Project description:The aim of the study is to identify genes and pathways associated with muscle and adipose wasting in PDAC cachexia. Muscle and adipose were collected from same individuals to study the concurrent muscle and adipose wasting.
2021-04-01 | GSE133979 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) causes involuntary wasting of adipose and muscle tissue, also known as cachexia. Cachexia is a major cause of cancer-related deaths, particularly among patients with PDAC. Here we profiled gene expression in adipose tissue and skeletal muscle in normal/sham control mice and in mice bearing orthotopic PDAC tumors. PDAC tumors were initiated by intra-pancreatic injection of a cell line derived from the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of pancreatic cancer, or by injection of the same cell line deleted for the IL6 gene using CRISPR/Cas9. KPC-IL6 knockout (ko) cells caused less adipose wasting and no muscle loss compared with KPC-wildtype (wt) cells.
2021-04-07 | GSE123310 | GEO
Project description:Background. Pancreatic Ductal AdenoCarcinoma (PDAC), the most frequent pancreatic cancer, is a deadly cancer since often diagnosed late and resistant to current therapies. A high proportion of PDAC patients are affected by cachexia induced by the tumor. This cachexia, characterized by loss of muscle mass and strength, contributes to patient frailty and poor therapeutic response. We showed that mitochondrial metabolism is reprogrammed in PDAC tumor cell and constitutes a vulnerability, opening novel therapeutic avenues. The objective of the present work was to investigate the molecular mechanisms underlying mitochondrial remodeling in PDAC cachectic skeletal muscle. Methods. Our study focused on the gastrocnemius muscle of genetically-engineered mice developing spontaneously a PDAC associated with cachexia (KIC GEMM). We compared KIC mice developing a pancreatic tumor in 9-10 weeks to control littermates. We did 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. Results. The cachectic KIC PDAC mice show a severe sarcopenia with loss of muscle mass and strength associated with a diminution in muscle fiber’s size and induction of protein degradation processes. Mitochondria in PDAC atrophic muscles show decreased respiratory capacities and structural alterations (“hyperfused” mitochondria), associated with deregulation of oxidative phosphorylation and mitochondrial dynamics pathways at the molecular level. Increased expression of multiple reactive oxygen species (ROS) defense genes suggests oxidative stress prone to affect mitochondrial macromolecules and homeostasis. Interestingly, multiple genes and proteins involved in DNA metabolism pathways, such as DNA damage, degradation of DNA, nucleotide synthesis, and folate pathway were found altered in sarcopenic mitochondria. While the number of mitochondria was not changed, the mitochondrial mass was decreased by a factor of 2 and the mitochondrial DNA by a factor of 3, suggesting a defect in mitochondrial genome homeostasis. Conclusions. We unveiled that 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, but concern also lipids, ROS and nucleic acids. Our data provide a frame to guide towards the most relevant molecular markers that would be affected at the start of tumor development and could be targets in the clinic to limit PDAC-induced cachexia at early stages of the pathology.
2024-04-09 | PXD036752 | Pride
Project description: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.
2024-03-11 | GSE226898 | GEO
Project description:Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, characterized by severe muscle and fat loss and yet, there are no biomarkers identified for this debilitating condition. Our objective was to identify circulating protein biomarkers using serum for human PDAC cachexia and understand their biological functions. Serum from 30 patients with PDAC was collected and protein profiles were generated using SOMAscan. The protein profiles were correlated with clinical variables such as Cancer associated weight loss (CAWL), body composition measurements of skeletal muscle index (SMI), skeletal muscle density (SMD), total adipose index (TAI) using Spearman’s correlation. Overall, 110 proteins of 1294 correlated with these clinical measures - 47 proteins for CAWL, 19 for SMI, 14 for SMD, and 30 for TAI (r-value 0.5, p<0.05). LYVE1, a homolog of CD44 implicated in tumor metastasis, was the top CAWL-associated protein (r= 0.67, p=0.0001). Protein co-expression network analysis identified immune system related pathways such as B-cell signaling, natural killer cell signaling, IL6 signaling in addition to identifying other known pathways in cachexia. Taken together, these data identify both immune system molecules and additional secreted factors and pathways not previously associated with PDAC and confirm the activation of previously identified pathways.
2020-12-31 | GSE119483 | GEO
Project description:Cancer-associated cachexia (CAC) is a metabolic syndrome characterized by progressive depletion of adipose and muscle tissue which cannot be corrected by conventional nutritional therapy. Adipose tissue, as an important energy storage, could appear obvious loss in early stage of CAC, which becomes a negative factor affecting the quality of life, efficacy of chemotherapy and so on. In order to identify differentially expressed RNAs in adipose tissue of CAC patients with noncachexia patients, we chose three gastric cancer patients with remarkable weight loss as CAC group and three gastric cancer patients without significant weight change within half a year as the control group. We resected a small subcutaneous adipose tissue from the abdomen of these six patients at time of surgery and completed transcriptome sequencing using Illumina platform. Compared with NCBI genome detabase, etc, we finally identified 386 differentially expressed mRNAs, 410 differentially expressed lncRNAs, 66 differentially expressed cirRNAs and 98 differentially expressed miRNAs. We hoped to provide more bases for follow-up study of adipose metabolism in cachexia.
2021-05-10 | GSE174128 | GEO
Project description:The regulatory gene pathways underlying the loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. Gene expression profiles (Human Gene 1.0 ST) of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (N=13) or without (N=14) cachexia. Data analyses were performed using the Affymetrix GeneChip Operating Software (GCOS) Version 1.4.
2010-04-10 | E-GEOD-20571 | biostudies-arrayexpress
Project description:Endothelial cells form a barrier between the contents of the blood and adipocytes. We hypothesized that during cancer cachexia development, transcriptomic changes alter angiocrine signals to contribute to adipose tissue remodelling. We used microarrays to observe changes in gene expression in endothelial cells isolated from subcutaneous fat of mice during pre-cachexia.
2023-06-19 | GSE212562 | GEO
Project description:Cancer cachexia represents a debilitating muscle wasting condition that is highly prevalent in patients with pancreatic ductal adenocarcinoma (PDAC). Cachexia is estimated to contribute to ~30% of cancer-related deaths, with deterioration of respiratory muscles suspected to be a key contributor to cachexia-associated morbidity and mortality. In recent studies, we identified inflammation and fibrotic remodeling of respiratory accessory muscles as a key feature of human PDAC cachexia. To gain insight into mechanisms driving respiratory muscle wasting and fibrotic remodeling in response to PDAC, we conducted temporal histological and transcriptomic analyses on diaphragm muscles harvested from mice bearing orthotopic murine pancreatic (KPC) tumors at time points reflective of pre-cachexia (D8 and D10), mild-moderate cachexia (D12 and D14) and advanced cachexia (endpoint). Compared to Sham, KPC mice showed progressive diaphragm myofiber atrophy beginning on D12 (-16 to -24% , D12toendpointvs.Sham,P< 0.05), which preceded reductions in breathing frequency (-55%,P= 0.0074) and diaphragm excursion (-43%,P= 0.0006) observed at endpoint. During the pre-cachexia phase, diaphragms showed significantleukocyte infiltration (+3 fold to +13-fold; D8–endpointvs.Sham,P< 0.05) and transcriptomic enrichment of inflammatory processes associated with tissue injury that remained increased through endpoint. Diaphragm inflammation was followed by increases in PDGFR+ fibroadipogenic progenitors (+2.5 to +3.8-fold; D10–endpointvs.Sham,P< 0.05), ECM expansion (+1.5 to +1.8-fold; D14–endpointvs.Sham),P<0.05) and collagen accumulation (+3.8-fold; Endpointvs.Sham,P= 0.0013). These processes were supported by changes in the diaphragm transcriptome. Ingenuity pathway analysis predicted factors involved in inflammatory responses to tissue injury, including TGF-B1, Angiotensin, and PDGF BB, as top upstream regulators activated in diaphragms prior to and throughout cachexia progression, while PGC-1α and the insulin receptor were among the top upstream regulators predicted to be suppressed. The transcriptomic dataset further revealed progressive disturbances to networks involved in lipid, glucose and oxidative metabolism, activation of the unfolded protein response and neuromuscular junction remodeling associated with denervation. In summary, our data support leukocyte infiltration and fibroadipogenic progenitor expansion as early events that precede wasting and fibrotic remodeling of respiratory muscles in response to PDAC that may also underlie metabolic disturbances, weakness and respiratory complications.
2025-01-01 | GSE271521 | GEO
Project description:Cancer cachexia, highly prevalent in lung cancer, is a debilitating syndrome characterized by involuntary loss of skeletal muscle mass, and is associated with poor clinical outcome, decreased survival and negative impact on on tumor therapy. Here we sought to identify the muscle gene profile and pathways regulated in cachexia. Vastus lateralis muscle was obtained of newly diagnosed treatment-naïve NSCLC patients with cachexia (n = 8) and matched healthy controls (n = 8). Self-reported weight loss and body composition measurements defined cachexia status. RNA sequencing was performed on the Illumina NovasSeq 6000.
2023-04-03 | E-MTAB-12781 | biostudies-arrayexpress