Exploring Bladder, Prostate, and Endometrial Cancer Risk in RRMS Patients: ATM, CREB1, and miR-19b-3p are Shared Biomarkers

Aim: Relapsing-remitting multiple sclerosis (RRMS) is the most common phenotype of MS. Bladder urothelial cancer (BLCA) is a highly prevalent malignancy of the urinary system. Prostate adenocarcinoma (PRAD) is the leading cause of cancer-related morbidity and mortality in males. Uterine corpus endometrial carcinoma (UCEC) is a prevalent malignancy in females. Identifying the risk of BLCA, PRAD, and UCEC in RRMS patients is crucial. This study aims to identify potential biomarkers that pose a risk for BLCA, PRAD, and UCEC in RRMS patients and have a common role. Materials and Methods: Expression profiles of RRMS patients were obtained from the GEO and ArrayExpress databases. Differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were identified using the Principal Component Analysis (PCA)-based Unsupervised-Feature-Extraction (UFE) method. GEO2R was applied to analyze datasets, and DEGs and DEMs were classified based on fold change. Target genes of up/downregulated DEMs were identified, and common gene clusters with corresponding up/downregulated DEGs were determined. Further bioinformatics analyses were conducted to identify hub-miRNAs and hub-genes. Results: 321 control and 293 RRMS samples were analyzed. DEMs and DEGs were identified using both the PCA-based UFE and GEO2R, and their intersections were determined. Target genes of DEMs were selected based on validation and prediction in at least two databases. Negatively correlated target genes of up/downregulated DEMs were identified, and common gene clusters were established. STRING analysis was performed, and a negative regulatory network was constructed using Cytoscape. Validation of hub-genes and hub-miRNAs in BLCA, PRAD, and UCEC was conducted using UALCAN and OncomiR. Discussion: Decreased ATM and CREB1 have been identified as direct targets of hsa-miR-19b-3p. They were identified as potential biomarkers in RRMS and further validated in BLCA, PRAD, and UCEC. This study highlights biomarkers in RRMS patients that may contribute to an increased risk of these cancers.