Pan-Cancer Analysis of the COVID-19 Causal Gene SLC6A20

[Image: see text] Genome-wide association studies demonstrated that the chromosome 3p31.21 locus was linked to the severity of COVID-19 disease. The SLC6A20 gene was reported to be one of the critical causal genes regulated by this locus. Various studies focused on demonstrating the severity of COVID-19 in cancer patients and reported that elevated SARS-CoV-2-associated gene expression might contribute to increased susceptibility for COVID-19 in cancer patients. Given that pan-cancer association for the COVID-19 causal gene SLC6A20 is lacking, we aimed to perform systematic profiling of SLC6A20 in different malignancies. Human Protein Atlas, UALCAN, and Hepatocellular Carcinoma (HCCDB) databases were used to assess SLC6A20 gene expression changes in The Cancer Genome Atlas samples with respect to their normal counterparts. GEPIA and TIMER2.0 databases were used to determine the correlation between SLC6A20 and COVID-19-associated genes. Different databases were used for identification of the correlation of SCL6A20 with infiltrating immune cells. The canSAR database was utilized to determine the association of SCL6A20 with immune profiling in different malignancies. The STRING database was utilized to determine the protein network interacting with SLC6A20. Here, we showed SLC6A20 mRNA expression in pan-cancer samples and their normal counterparts. Increased SCL6A20 expression was associated with tumor grade, and there was a positive correlation with SARS-CoV-2-associated genes. Furthermore, SLC6A20 expression was positively correlated with infiltrating neutrophils and immune-related signatures. Lastly, SLC6A20 expression was found to be associated with the angiotensin converting enzyme 2 homologue, TMEM27, suggesting a potential link between SLC6A20 and COVID-19. Taken together, these results suggest that elevated SLC6A20 levels might be partly responsible for increased susceptibility of cancer patients to COVID-19 disease. Therapeutic intervention strategies against SLC6A20 in cancer patients, alongside other treatment modalities, might offer a benefit in delaying COVID-19 disease.