Identify and validate RUNX2 and LAMA2 as novel prognostic signatures and correlate with immune infiltrates in bladder cancer.

Background: Muscle-invasive bladder cancer (MIBC) develops lymph node (LN) metastasis or distant metastasis, leading to recurrence and poor prognosis. The five-year survival rate of MIBC with LN or distant metastasis is only 8.1%; therefore, there is an urgent need to identify reliable biomarkers for prognosis and treatment regimen for patients with bladder cancer (BLCA). Methods: SEER database was used to select important clinical characteristics for MIBC. Then, weighted gene co-expression network analysis (WGCNA) was employed to identify differentially expressed genes (DEGs) to recognize significant co-expression modules by calculating the correlation between the modules and clinical data. Furthermore, Cox regression and lasso analysis were applied to screen prognostic hub genes and establish the risk predictive model. Bladder cancer cell lines (UMUC3 and 5637) were used for experimental validation Results: Cox analysis of 122,600 MIBC patients showed that the N stage was the most important clinical factor. A total of 4,597 DEGs were calculated between N0 and N+ patients, and WGCNA with these DEGs in 368 samples revealed that expression of turquoise was positively and strongly correlated with the N stage. Eight genes were identified as important prognostic candidates using lasso regression based on Cox analysis and STRING database. Combining GEO datasets, literature, and clinical factors, we identified Conclusions: We constructed a new eight-gene risk model to provide novel prognostic biomarkers and therapeutic targets for BLCA.