Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq of vastus lateralis muscle biopsies of newly diagnosed treatment-naïve NSCLC patients with cachexia and age-matched and sex-matched healthy controls

ABSTRACT: 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.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Wouter Worp

PROVIDER: E-MTAB-12781 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Nuclear transcription factor κ B activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia.

Op den Kamp Céline M CM Langen Ramon C RC Snepvangers Frank J FJ de Theije Chiel C CC Schellekens Johanna M JM Laugs Fabian F Dingemans Anne-Marie C AM Schols Annemie M AM

The American journal of clinical nutrition 20130731 3

<h4>Background</h4>Experimental models of cancer cachexia have indicated that systemic inflammation induces muscle-protein breakdown and wasting via muscular nuclear transcription factor κB (NF-κB) activation. This process may limit the efficacy of nutritional intervention.<h4>Objectives</h4>We assessed muscle NF-κB activity and protein turnover signaling in progressive stages of clinical lung cancer cachexia and assessed whether circulating factors can induce muscular NF-κB activity.<h4>Design< ...[more]

PMID: 23902785

Publication: 1/2

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Project description:Background Loss of skeletal muscle mass in advanced cancer is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are still lacking. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in muscle proteome and secretome associated with cancer-induced cachexia to better understand cellular mechanisms involved in this wasting process and to identify secreted proteins which might reflect the ongoing muscle atrophy process. Methods We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Selected reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Their muscle source was demonstrated by assessing their gene expression in skeletal muscle and in cultured myotubes. Finally, we also investigated their regulation in muscle cells. Alterations in several molecular pathways potentially involved in muscle atrophy were highlighted using Gene ontology enrichment analyses. Results Our results revealed a dramatic increased production (2-to 25-fold) by the muscle of several acute phase reactants (APR: Haptoglobin, Serpina3n, Complement C3, Serum amyloid A1) which are also released in the circulation during C26 cancer cachexia. Their production was confirmed in other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Glucocorticoids and pro-inflammatory cytokines contribute directly to their increased expression in muscle cells in vitro, while the role of IL-6 in the muscular induction of these APR was demonstrated in vivo. Conclusions Cancer is associated with marked changes in muscle secretome during muscle wasting. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.

Dataset Information

RNA-seq of vastus lateralis muscle biopsies of newly diagnosed treatment-naïve NSCLC patients with cachexia and age-matched and sex-matched healthy controls

Publications

Nuclear transcription factor κ B activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia.

Similar Datasets

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