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BackgroundThe relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM.MethodsThe Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan–Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT. In vitro assays were used to further confirm the function of S100A6 in PC.ResultsWGCNA recognized three major modules for T2DM and two major modules for PC. There were 44 shared genes identified for PC and T2DM, and Gene Ontology (GO) analysis showed that regulation of endodermal cell fate specification was primarily enriched. In addition, a key shared gene S100A6 was derived in the validation tests. S100A6 was shown to be highly expressed in PC compared to non-tumor tissues. PC patients with high S100A6 expression had worse overall survival (OS) than those with low expression. GSEA revealed that S100A6 is involved in cancer-related pathways and glycometabolism-related pathways. There is a strong relationship between S100A6 and TIME. In vitro functional assays showed that S100A6 helped to induce the PC cells’ proliferation and migration. We also proposed a diagram of common mechanisms of PC and T2DM.ConclusionsThis study firstly revealed that the regulation of endodermal cell fate specification may be common pathogenesis of PC and T2DM and identified S100A6 as a possible biomarker and therapeutic target for PC and T2DM patients.
Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The proteinprotein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. The CYCS and ESRRA may play significant roles in the progression of skeletal muscle aging and serve as potential biomarkers for future diagnosis and treatment.
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