Aberrant Mitochondrial Homeostasis at the Crossroad of Musculoskeletal Ageing and Non-Small Cell Lung Cancer

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 (PPI) networks and 35 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, MRPS26, MRPS17, MRPL18, and 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 microenvironment in ageing muscle and NSLC. Further studies comparing changes in sarcopenia and NSCL associated cachexia are warranted.