Society of Meta-Research and Biomedical Innovation, London, United Kingdom.
Department of Musculoskeletal Biology, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
PLoS One. 2022 Sep 6;17(9):e0273766. doi: 10.1371/journal.pone.0273766. eCollection 2022.
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.
癌症恶病质伴随着肌肉萎缩，与衰老相关性肌肉减少症（sarcopenia）共享多种共同的分解代谢途径，包括线粒体功能障碍。本研究调查了有衰老相关性肌肉减少症风险的老年健康成年人的骨骼肌组织的基因表达，以确定潜在的基因生物标志物，这些标志物的表达失调及其蛋白干扰参与非小细胞肺癌（NSCLC）。文献筛选产生了 14 个微阵列数据集（骨骼肌老化的 GSE25941、GSE28392、GSE28422、GSE47881、GSE47969 和 GSE59880；NSCLC 的 GSE118370、GSE33532、GSE19804、GSE18842、GSE27262、GSE19188、GSE31210 和 GSE40791）。差异表达基因（DEGs）用于构建蛋白质-蛋白质相互作用网络并检索聚类基因模块。根据 11 种拓扑算法对重叠模块 DEGs 进行排序，并与 NSCLC 的预后、组织表达和肿瘤纯度相关。分析表明，哺乳动物线粒体核糖体蛋白（MRPS26、MRPS17、MRPL18 和 MRPL51）的失调表达与 NSCLC 患者的生存率降低和肿瘤纯度降低相关，而同一基因在健康老年人群中的组织表达则呈相反方向。这些结果支持衰老肌肉中线粒体核糖体微环境与 NSCLC 之间的潜在联系。需要进一步比较与肌肉减少症和 NSCLC 相关恶病质相关的变化的研究。
