Aberrant mitochondrial homeostasis at the crossroad of musculoskeletal ageing and non-small cell lung cancer.



Prokopidis, Konstantinos ORCID: 0000-0002-6264-9388, Giannos, Panagiotis, Witard, Oliver C, Peckham, Daniel and Ispoglou, Theocharis
(2022) Aberrant mitochondrial homeostasis at the crossroad of musculoskeletal ageing and non-small cell lung cancer. PloS one, 17 (9). e0273766-e0273766.

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Abstract

Cancer cachexia is accompanied by muscle atrophy, sharing multiple common catabolic pathways with sarcopenia, including mitochondrial dysfunction. This study investigated gene expression from skeletal muscle tissues of older healthy adults, who are at risk of age-related sarcopenia, to identify potential gene biomarkers whose dysregulated expression and protein interference were involved in non-small cell lung cancer (NSCLC). Screening of the literature resulted in 14 microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880 in musculoskeletal ageing; GSE118370, GSE33532, GSE19804, GSE18842, GSE27262, GSE19188, GSE31210, GSE40791 in NSCLC). Differentially expressed genes (DEGs) were used to construct protein-protein interaction networks and retrieve clustering gene modules. Overlapping module DEGs were ranked based on 11 topological algorithms and were correlated with prognosis, tissue expression, and tumour purity in NSCLC. The analysis revealed that the dysregulated expression of the mammalian mitochondrial ribosomal proteins, Mitochondrial Ribosomal Protein S26 (MRPS26), Mitochondrial Ribosomal Protein S17 (MRPS17), Mitochondrial Ribosomal Protein L18 (MRPL18) and Mitochondrial Ribosomal Protein L51 (MRPL51) were linked to reduced survival and tumour purity in NSCLC while tissue expression of the same genes followed an opposite direction in healthy older adults. These results support a potential link between the mitochondrial ribosomal microenvironment in ageing muscle and NSCLC. Further studies comparing changes in sarcopenia and NSCLC associated cachexia are warranted.

Item Type: Article
Uncontrolled Keywords: Mitochondria, Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cachexia, Ribosomal Proteins, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Aging, Homeostasis, Aged, Sarcopenia, Tumor Microenvironment
Depositing User: Symplectic Admin
Date Deposited: 13 Dec 2022 11:41
Last Modified: 06 May 2023 00:36
DOI: 10.1371/journal.pone.0273766
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3166627