Single-cell RNA sequencing identifies SLC6A3 as a biomarker and prognostic marker in clear cell renal cell carcinoma

Background The SLC6A3 gene encodes dopamine protein and is a member of the sodium and chloride-dependent neurotransmitter transporter family. While the role of SLC6A3 in Parkinson’s disease is well established, its function in cancer, especially in clear cell renal cell carcinoma (ccRCC), remains unclear. Methods To investigate the expression and function of SLC6A3 in ccRCC, we conducted a study using single-cell transcriptomics and bulk RNA sequencing data. We analyzed advanced ccRCC single-cell RNA sequencing profiles, bulk RNA sequencing, and microarray data to assess the expression of SLC6A3 in tumor cells, benign kidney tubule cells, and immune cells. Results Our analysis showed that SLC6A3 expression is specific to ccRCC tumor cells and is not present in benign kidney tubule cells or immune cells of benign kidney and kidney tumors. Further, we found an elevated expression of SLC6A3 in ccRCC tumors compared to the benign kidney. Receiver operating characteristics analysis suggests that SLC6A3 is highly sensitive and specific to ccRCC. Additionally, we found a correlation between HNF4A signaling and SLC6A3 expression in two independent mRNA expression profiles. Interestingly, elevated expression of SLC6A3 is a predictor of better overall and progression-free survival of ccRCC patients. Conclusions Our findings suggest that SLC6A3 is a potential diagnostic and prognostic marker for ccRCC. The study highlights the importance of understanding the role of SLC6A3 in cancer and provides new insights into ccRCC diagnosis and treatment.