Beschreibung:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>The epidemiological investigation of different cancer types in the global population has reported a decreased risk of bladder cancer (BLCA) in Parkinson’s diseases (PD). <jats:italic>SNCA</jats:italic> a critical gene in PD pathology have been reported involved in tumorigenesis recently. However, the role of <jats:italic>SNCA</jats:italic> in BLCA remains unclear. This study aimed to explore the potential value of <jats:italic>SNCA</jats:italic> as a prognostic diagnostic molecular biomarker in BLCA.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>In this study, we explored the expression pattern, prognostic value and promoter methylation level of <jats:italic>SNCA</jats:italic> in BLCA by GEPIA2, UALCAN, TCGA, GENT2, GEO and c-BioPortal database. Then, we used LinkedOmics database to obtain the co-expression genes of <jats:italic>SNCA</jats:italic> for further study by WGCNA. We further investigated the correlations between <jats:italic>SNCA</jats:italic> expression and six main types of immune cell infiltrations and immune signatures by TIMER. Finally, BLCA cell lines treated with 5-Aza-CdR were used to explore the correlation between increased methylation and downregulated mRNA expression.</jats:p>
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<jats:title>Results</jats:title>
<jats:p><jats:italic>SNCA</jats:italic> was downregulated in tumor tissues in TCGA-BLCA, GENT2 and GEO, which was validated in our cohort by qRT-PCR and immunohistochemistry. <jats:italic>SNCA</jats:italic> was confirmed as an independent predictor of poor overall survival (OS). LinkedOmics analysis suggested that <jats:italic>SNCA</jats:italic> regulates cell adhesion molecules, cytokine–cytokine receptor interaction, and complement and coagulation cascades. Twenty-two co-expression gene modules were constructed by WGCNA, and most of them were significantly associated with OS and disease-free survival (DFS). Six key genes (<jats:italic>CNTN1</jats:italic>, <jats:italic>DACT3</jats:italic>, <jats:italic>MYLK1</jats:italic>, <jats:italic>PDE2A</jats:italic>, <jats:italic>RBM24</jats:italic>, and <jats:italic>ST6GALNAC3</jats:italic>) screened also significantly correlated with prognosis. There were significant correlations between <jats:italic>SNCA</jats:italic> expression and immune infiltrations, especially T cell, suggesting that immune infiltration was one of the reasons for the influence of <jats:italic>SNCA</jats:italic> on prognosis in BLCA. Analysis by ULACAN and c-BioPortal showed that the promoter methylation of <jats:italic>SNCA</jats:italic> negatively correlated with its mRNA level. Furthermore, BLCA cell treatment with 5-Aza-CdR revealed that <jats:italic>SNCA</jats:italic> expression levels were upregulated with decreased methylation.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>Our research showed that <jats:italic>SNCA</jats:italic> was downregulated in BLCA and negatively correlation with DNA methylation. High <jats:italic>SNCA</jats:italic> expression was confirmed as an independent risk for prognosis. <jats:italic>SNCA</jats:italic> probably plays an important role in the infiltration of immune cells, especially with T cells. Thus, <jats:italic>SNCA</jats:italic> may be a promising prognostic biomarker in BLCA patients.</jats:p>
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