BackgroundThe predominant and most prevalent form of metastatic bladder cancer (BCa) is lymphatic metastasis, which is associated with a highly dismal prognosis for patients. Aging-related genes (ARGs) are believed to contribute significantly to tumor development. However, the effect of ARGs on lymphatic metastasis of BCa is unclear. This research sought to establish a prognosis model based on ARGs associated with lymphatic metastasis in BCa.MethodsWe downloaded BCa data from the TCGA and GEO databases and ARGs from the Aging Atlas database. The least absolute shrinkage and selection operator (LASSO) approach was applied to obtain the characteristic ARGs of risk signature in the TCGA cohort. Verification was done using the GSE13507 dataset. The R package ‘ConsensusClusterPlus’ was employed to identify the molecular subtypes based on the characteristic ARGs. Protein-Protein interaction network, MCODE analysis, enrichment analysis (KEGG, GO, GSEA), and immune infiltration analysis were performed to investigate underlying mechanisms. EdU, migration and invasion assays, wound healing assays, immunofluorescence staining, and quantitative polymerase chain reaction were conducted to evaluate the impact of ELN on the proliferative, migratory, and invasive capacities of BCa cells.ResultsWe identified 20 differently expressed ARGs. A four ARGs risk signature (EFEMP1, UCHL1, TP63, ELN) was constructed in the TCGA cohort. The high-risk group (category) recorded a reduced overall survival (OS) rate relative to the low-risk category (hazard ratio, 2.15; P <0.001). The risk score could predict lymphatic metastasis in TCGA cohort (AUC=0.67). The GSE13507 dataset was employed to verify the validity of this risk score. Based on the four ARGs, two distinct aging profiles (Cluster 1 and Cluster 2) were discovered utilizing the ConsensusClusterPlus, and Cluster 2 possessed a favorable OS in contrast with Cluster 1 (hazard ratio, 0.69; P =0.02). Classical tumor signaling pathways, ECM-associated signaling pathways, and immune-related signaling pathways participate in BCa progression. ELN recombinant protein affected the expression of collagen and increased migration and invasiveness in BCa cells.ConclusionWe constructed a four-ARG risk signature and identified two aging molecular subtypes. This signature could serve as an effective survival predictor for patients with BCa.

Diabetes can cause erectile dysfunction (ED) in more than half of male patients. However, the mechanisms underlying diabetes-induced erectile dysfunction (DED) remain unknown. This study is aimed at systematically analyzing the cellular and molecular mechanisms leading to DED using bioinformatic analysis and providing molecular targets for predicting and treating DED. In total, we identified 800 DEGs in the DED samples compared with those in the control group. The 407 upregulated DEGs were mainly enriched in glucose and lipid metabolism-related pathways, and the 393 downregulated DEGs were primarily enriched in tissue development and structure. Dysregulated extracellular matrix genes (especially collagen and elastin) may be closely related to damage to the erectile function of the corpus cavernosum. Sixteen hub genes and 24 modules were detected with hub genes and MCODE analysis. The consensus sequence AAA (G/C) AAA was observed at the promoter sites of most genes that were enriched in the “posttranslational protein phosphorylation” pathway. These genes had abundant phosphorylation sites. Furthermore, 20 TFs targeting DEGs were identified using ChEA3 tool. In conclusion, our research comprehensively and systematically describes the molecular characteristics of DED and suggests that dysregulated extracellular matrix genes and protein phosphorylation may play critical roles in DED. Therefore, they may be potential markers for diagnosing and treating DED.