Hub gene associated with prognosis in bladder cancer is a novel therapeutic target.

Objective: Bladder cancer is a clinical and social conundrum due to its high incidence and recurrence rate. It is urgent to find new targets for the diagnosis and treatment of bladder cancer and improve the prognosis and survival rate of bladder cancer patients. We sought a prognosis-related gene, built related models of evaluated bladder cancer and identified the function of the hub gene in bladder cancer. Methods: We downloaded the data of bladder cancer patients from the TCGA database, and used differentially expressed genes (DEGs), copy number variation (CNV) and survival analysis to scan the hub genes associated with prognosis in bladder cancer. Then, multi-factor cox regression was used to obtain the bladder cancer prognosis correlation model. Then, we analyzed the relationship between the expression of hub gene and immune microenvironment of bladder cancer. The relationship between the expression of hub gene and prognosis in bladder cancer patients was verified by immunohistochemistry. Cell proliferation assay and drug sensitivity test in vivo were used to verify the inhibition of bladder cancer by targeted inhibitors. Results: In bladder cancer, we screened seven hub genes (ACLY, CNP, NKIRAS2, P3H4, PDIA6, VPS25 and XPO1) associated with survival. Moreover, the multifactor regression model constructed with hub gene can well distinguish the prognosis of bladder cancer. Hub gene is mostly associated with immune microenvironment. Immunohistochemical results basically confirmed the importance of XPO1 in bladder cancer. Selinexor (an inhibitor of XPO1) could effectively inhibit the proliferation of bladder cancer in the cell proliferation experiments by CCK-8 assays and it could suppress the growth of bladder cancer in mouse bladder cancer model. Conclusions: In this study, a prognostic model with seven hub genes has provided great help for the prognosis prediction of bladder cancer patients. And XPO1 is an important target affecting the prognosis of bladder cancer, and inhibition of XPO1 can effectively inhibit bladder cancer proliferation and growth.

Analysis of key genes reveal lysine demethylase 5B promotes prostate cancer progression.

Prostate cancer (PCa) is one of the most common types of cancer in males globally. However, the molecular mechanisms underlying PCa progression remain largely unclear. In the present study, Gene Expression Omnibus (GEO) datasets and datasets from The Cancer Genome Atlas (TCGA) were used to analyze the expression of lysine demethylase 5B (KDM5B) in PCa. Proliferation, cell cycle and migration assays were used to detect the functional roles of KDM5B. It was found KDM5B was upregulated in PCa tissues by analyzing GEO and TCGA datasets. KDM5B knockdown significantly suppressed proliferation and cell cycle progression in PCa cells. In additional, KDM5B knockdown inhibited PCa cell migration. By analyzing a TCGA dataset, KDM5B was found to be upregulated in patients at N1 stage compared with N0 stage PCa, in patients at T3+T4 stages compared with T2 stage and in patients with Gleason score ≥8 compared with those with score ≤7. Kaplan-Meier analysis revealed that higher expression of KDM5B was associated with shorter biochemical recurrence-free survival and overall survival time in patients with PCa. These results suggest that expression of KDM5B may serve as a biomarker to predict the outcome of PCa.