A Three Protein-Coding Gene Prognostic Model Predicts Overall Survival in Bladder Cancer Patients

Abstract

Bladder cancer (BLCA) is the most common urinary tract tumor and is the 11th most malignant cancer worldwide. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified. In this study, we focused on the role of protein-coding gene methylation in the prognosis of BLCA. We downloaded BLCA clinical and methylation data from The Cancer Genome Atlas (TCGA) database and used this information to identify differentially methylated genes and construct a survival model using lasso regression. We assessed 365 cases, with complete information regarding survival status, survival time longer than 30 days, age, gender, and tumor characteristics (grade, stage, T, M, N), in our study. We identified 353 differentially methylated genes, including 50 hypomethylated genes and 303 hypermethylated genes. After annotation, a total of 227 genes were differentially expressed. Of these, 165 were protein-coding genes. Three genes (zinc finger protein 382 (ZNF382), galanin receptor 1 (GALR1), and structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1)) were selected for the final risk model. Patients with higher-risk scores represent poorer survival than patients with lower-risk scores in the training set ( HR = 2.37 , 95% CI 1.43-3.94, p = 0.001 ), in the testing group ( HR = 1.85 , 95% CI 1.16-2.94, p = 0.01 ), and in the total cohort ( HR = 2.06 , 95% CI 1.46-2.90, p < 0.001 ). Further univariate and multivariate analyses using the Cox regression method were conducted in these three groups, respectively. All the results indicated that risk score was an independent risk factor for BLCA. Our study screened the different methylation protein-coding genes in the BLCA tissues and constructed a robust risk model for predicting the outcome of BLCA patients. Moreover, these three genes may function in the mechanism of development and progression of BLCA, which should be fully clarified in the future.

The Galaninergic System: A Target for Cancer Treatment

“…GAL 1 R DNA methylation is among the most epigenetic molecular alterations in endometrial cancer; this methylation indicates malignancy with a high degree of sensitivity and specificity [ 208 ]. The methylation of the GAL 1 R gene in bladder cancer has been involved in the prognosis of the disease, but the role played by the galaninergic system in this cancer is currently unknown [ 209 ].…”

Low Levels of TRIM28-Interacting KRAB-ZNF Genes Associate with Cancer Stemness and Predict Poor Prognosis of Kidney Renal Clear Cell Carcinoma Patients

“…Recently, ZNF382 was reported as a component of an epigenetic signature that predicts the survival of laryngeal squamous cell carcinoma [ 53 ]. Moreover, with two other protein-coding genes, ZNF382 forms a prognostic signature that robustly predicts the outcome of bladder cancer patients [ 54 ]. Distinct methylation pattern of ZNF382 promoter might serve as a biomarker in pancreatic ductal carcinoma [ 55 ].…”

An interactive nomogram based on clinical and molecular signatures to predict prognosis in multiple myeloma patients

“…High levels of ANLN contributed to the poor prognosis of anthracycline-based chemotherapy in breast cancer patients [ 53 , 54 ]. A three protein-coding genes prognostic model including SMCHD1 predicts overall survival in bladder cancer patients [ 55 ]. Univariate and multivariate survival analysis showed that high expression of HAUS3 was an independent prognostic factor for the dismal outcome of overall survival of HCC patients [ 55 ].…”

“…A three protein-coding genes prognostic model including SMCHD1 predicts overall survival in bladder cancer patients [ 55 ]. Univariate and multivariate survival analysis showed that high expression of HAUS3 was an independent prognostic factor for the dismal outcome of overall survival of HCC patients [ 55 ]. High expression of HAUS3 is also associated with poor prognosis and HCC progression [ 56 ].…”