Molecular Subtypes of Human Skeletal Muscle in Cancer Cachexia
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PROVIDER: PRJNA1072128 | ENA |
REPOSITORIES: ENA
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Project description:Molecular Subtypes of Human Skeletal Muscle in Cancer Cachexia
| PRJNA1236392 | ENA
Project description:Molecular Subtypes of Human Skeletal Muscle in Cancer Cachexia
| PRJNA1072130 | ENA
Project description:Molecular Subtypes of Human Skeletal Muscle in Cancer Cachexia
| PRJNA1236386 | ENA
Project description:Cancer-associated muscle wasting associates with poor clinical outcomes1, but its underlying biology is largely uncharted in humans2. Unbiased RNAome analysis (coding and non-coding RNAs) with unsupervised clustering using Integrative Non-negative Matrix Factorization (intNMF)3 provides an avenue to identify distinct molecular subtypes, here applied to muscle of patients with colorectal or pancreatic cancer. Rectus abdominis biopsies from 84 patients was profiled using high-throughput next generation sequencing. Here we show that intNMF with stringent quality metrics of clustering identifies 2 highly coherent molecular subtypes within muscle of patients with cancer. Patients in Subtype 1 (vs Subtype 2) showed clinical manifestations of cachexia: high-grade weight loss, low muscle mass, atrophy of Type IIA and Type IIX muscle fibres and reduced survival. Based on differential expression between the subtypes, our results indicate biological processes that may contribute to cancer-associated loss of muscle mass and function, including altered post-transcriptional regulation, and perturbation of neuronal systems, cytokine storm/cellular immune response, extracellular matrix, and metabolic abnormalities spanning xenobiotic metabolism, hemostasis, signal transduction, embryonic/pluripotent stem cells, and amino acid metabolism. Differential expression between subtypes indicates involvement of multiple, intertwined higher-order gene regulatory networks, suggesting potential for interacting (hub)lncRNA-miRNA-mRNA interaction networks as targets for future research.
2025-07-17 | GSE254877 | GEO
Project description:Cancer-associated muscle wasting associates with poor clinical outcomes1, but its underlying biology is largely uncharted in humans2. Unbiased RNAome analysis (coding and non-coding RNAs) with unsupervised clustering using Integrative Non-negative Matrix Factorization (intNMF)3 provides an avenue to identify distinct molecular subtypes, here applied to muscle of patients with colorectal or pancreatic cancer. Rectus abdominis biopsies from 84 patients was profiled using high-throughput next generation sequencing. Here we show that intNMF with stringent quality metrics of clustering identifies 2 highly coherent molecular subtypes within muscle of patients with cancer. Patients in Subtype 1 (vs Subtype 2) showed clinical manifestations of cachexia: high-grade weight loss, low muscle mass, atrophy of Type IIA and Type IIX muscle fibres and reduced survival. Based on differential expression between the subtypes, our results indicate biological processes that may contribute to cancer-associated loss of muscle mass and function, including altered post-transcriptional regulation, and perturbation of neuronal systems, cytokine storm/cellular immune response, extracellular matrix, and metabolic abnormalities spanning xenobiotic metabolism, hemostasis, signal transduction, embryonic/pluripotent stem cells, and amino acid metabolism. Differential expression between subtypes indicates involvement of multiple, intertwined higher-order gene regulatory networks, suggesting potential for interacting (hub)lncRNA-miRNA-mRNA interaction networks as targets for future research.
2025-07-17 | GSE254878 | GEO
Project description:Cancer-associated muscle wasting associates with poor clinical outcomes1, but its underlying biology is largely uncharted in humans2. Unbiased RNAome analysis (coding and non-coding RNAs) with unsupervised clustering using Integrative Non-negative Matrix Factorization (intNMF)3 provides an avenue to identify distinct molecular subtypes, here applied to muscle of patients with colorectal or pancreatic cancer. Rectus abdominis biopsies from 84 patients was profiled using high-throughput next generation sequencing. Here we show that intNMF with stringent quality metrics of clustering identifies 2 highly coherent molecular subtypes within muscle of patients with cancer. Patients in Subtype 1 (vs Subtype 2) showed clinical manifestations of cachexia: high-grade weight loss, low muscle mass, atrophy of Type IIA and Type IIX muscle fibres and reduced survival. Based on differential expression between the subtypes, our results indicate biological processes that may contribute to cancer-associated loss of muscle mass and function, including altered post-transcriptional regulation, and perturbation of neuronal systems, cytokine storm/cellular immune response, extracellular matrix, and metabolic abnormalities spanning xenobiotic metabolism, hemostasis, signal transduction, embryonic/pluripotent stem cells, and amino acid metabolism. Differential expression between subtypes indicates involvement of multiple, intertwined higher-order gene regulatory networks, suggesting potential for interacting (hub)lncRNA-miRNA-mRNA interaction networks as targets for future research.
2025-07-17 | GSE292052 | GEO
Project description:Cachexia is a systemic metabolic syndrome characterized by loss of fat and skeletal muscle mass in chronic wasting diseases such as cancer. The regulation of cellular protein synthesis in response to workload in skeletal muscle is generally blunted in cancer cachexia; however, the precise molecular regulation is largely unknown. In this study, to examine the molecular mechanism of skeletal muscle protein metabolism in cancer cachexia, we analyzed comprehensive gene expression in skeletal muscle using microarrays. CD2F1 mice (male, 7 weeks old) were subcutaneously transplanted (1*10^6 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Functional overload of the plantaris muscle by synergist ablation was performed at the 2nd week, and the plantaris muscle was sampled at the 4th week of cancer transplantation. The hypertrophy of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mTOR signaling) associated with compensatory overload was significantly suppressed with the cancer cachexia. Gene expression profiling and pathway analysis by microarray showed that resistance to muscle protein synthesis associated with cancer cachexia was induced by downregulation of insulin-like growth factor-1. These observations show that cancer cachexia induces resistance to muscle protein synthesis, which could be a potential factor inhibiting the adaptation of skeletal muscle growth to physical exercise.
2021-10-15 | GSE185934 | GEO
Project description:Cancer cachexia is a multifactorial wasting syndrome affecting body and lean tissue mass that is often exacerbated by anticancer chemotherapy. In this study, we used a mouse model of acute myeloid leukemia chemotherapy induction regimen (CIR) comprising daunorubicin and cytarabine to investigate the molecular mechanisms underlying cachexia. Quantitative tandem mass tag (TMT) based proteomics was performed on skeletal muscle (quadriceps) to uncover biomarkers and pathways associated with chemotherapy induced muscle wasting. Our findings demonstrate that the AML CIR induced an acute cachexic phenotype characterized by approximately 10 percent body and lean mass loss and 20 percent muscle fibre atrophy. Through deep proteome profiling, two potential biomarkers—haptoglobin (Hp) and glutamine synthetase (Glul)—were identified. Haptoglobin in particular was responsive to cachexia severity, recovery, and exacerbation via exercise, indicating its potential as a conditionally sensitive biomarker of muscle wasting. Pathway analysis revealed upregulation of mitochondrial metabolism including branched chain amino acid catabolism and mitochondrial uncoupling proteins (Ucp1 and Ucp3), suggesting hypermetabolism as a key driver of the phenotype. These data support the use of skeletal muscle proteomics in characterizing chemotherapy induced cachexia and identifying sensitive muscle specific biomarkers for future translational and therapeutic studies.
2025-06-16 | PXD063910 | Pride
Project description:Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-induced gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. shRNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of cancer cachexia-induced muscle atrophy and highlight potential therapeutic targets for this disorder.
2024-07-12 | GSE272083 | GEO
Project description:Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-induced gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. shRNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of cancer cachexia-induced muscle atrophy and highlight potential therapeutic targets for this disorder.
2024-07-12 | GSE272084 | GEO