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.
Highlights
Bladder cancer (BLCA) is the most common urinary tract tumor and the 11th most malignant tumor worldwide
We describe a new risk model including protein-coding gene methylation which may improve the methods of predicting BLCA prognosis but can screen genes with clear biological effects, which will help in identifying the mechanisms involved in BLCA development and progression
Four hundred and twelve cases of clinical data from patients with BLCA were downloaded from TGCA database
Summary
Bladder cancer (BLCA) is the most common urinary tract tumor and the 11th most malignant tumor worldwide. Muscle invasive bladder cancer (MIBC) is a more aggressive form of the disease, with a 5-year survival rate of approximately 60% in patients with local disease and less than 5% in patients with distant metastasis [2]. The classical factors that are closely associated with the prognosis of BLCA include tumor clinical stage, tumor grade, carcinoma in situ, and distant metastasis. The study of molecular markers to predict the prognosis of BLCA has expanded and has focused mainly on DNA alterations, such as DNA polymorphisms, mutations, and mRNA and protein expression levels [3]. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified [4]. Molecular biomarkers can effectively improve the accuracy of prognosis prediction and may highlight tumorigenic characteristics that are helpful for the development of novel therapies, as well as identifying mechanisms underpinning the development and progression of diseases
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