Identification and construction of prognostic clusters and risk-prognosis model based on aging-immune related genes...

Faced with the current global ageing situation, advanced age has become a risk factor for bladder carcinogenesis progression and immunotherapy. Exploring the common mechanisms of aging and immune in bladder cancer and finding new prognostic markers and immunotherapeutic targets has become an urgent issue.

Aging-immune related genes (AIGs) were collected from the public databases MSIGDB, HAGR and ImmPort, and hub AIGs were finally identified in the TCGA-BLCA disease cohort by expression, prognosis, and clinicopathological correlation analysis, and the correlation of hub AIGs with immune microenvironment, immunotherapeutic response, ferroptosis and m6A methylation was verified. Subsequently, prognostic clusters and risk-prognosis models for AIGs was constructed by cluster analysis and multifactorial Cox regression analysis, and the gene mutation and immune infiltration characteristics of the different clusters were explored. Finally, the expression level of related genes was verified by immunohistochemical experiments using patient samples from our medical center.

145 potential prognostic AIGs were collected in bladder cancer and finally clarified NFKB1 and IL7 with significant expression differences, prognostic value and age correlation. By single gene analysis, hub AIGs were explored to be significantly correlated with immunotherapeutic response, immune microenvironment, ferroptosis and m6A methylation. Subsequently, the risk-prognosis model was constructed with Riskscore = (0.0581)*NFKB1 + (- 0.2285)*IL7. And prognostic clusters based on hub AIGs was performed by cluster analysis, which clarified that the high-risk group was the pro-cancer group, which had a lower mutation rate of hub genes and higher of neutrophil infiltration. Finally, immunohistochemistry of patients confirmed that IL7 and NFKB1 were underexpressed in bladder cancer, and the proliferation and migration ability of tumor cells were significantly decreased after overexpression of these genes.

This study is the first to identify NFKB1 and IL7 as hub AIGs in bladder cancer, which provide new prognostic markers and immunotherapeutic targets.