SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer.

Background: Overexpression of SLC16A3 can contribute to the development of various tumors by regulating metabolism, but a systematic analysis of SLC16A3 in bladder cancer (BC) has been rarely reported.

Methods: We used the BC datasets from public databases to investigate SLC16A3 expression in BC. We first analysed the relationship between SLC16A3 expression and clinical characteristics of 412 bladder cancer patients. After that, gene function analyses and immunocorrelation analyses of SLC16A3 were conducted with the R package. For immunotherapy effect and drug sensitivity analysis, we also used the R package. We also analysed the relation between SLC16A3 expression and 20 m6A modification key genes. Finally, we determined the expression localization of SLC16A3 in bladder cancer by single-cell sequencing analysis using 3,115 BC cells. We further detected the expression of SLC16A3/MCT4 on BC samples by reversed transcriptionquantitative polymerase chain reaction and immunohistochemistry.

Results: The SLC16A3 was overexpressed in BC cells, including epithelial cells (p＜0.001). The high SLC16A3 expression level of patients with BC was significantly related to poor prognosis (p＝0.044), and we established a reliable prognosis model for BC patients. Statistically significant associations between SLC16A3 and m6A modification (ALKBH5) gene (p＜0.001), key genes in aerobic glycolysis, M2 macrophage infiltration (p＝0.0058), and immune checkpoint regulation were observed.

Conclusion: Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.