Pan-cancer analysis of promoter activity quantitative trait loci

Abstract

Abstract Altered promoter activity has been generally observed in diverse biological processes, including tumorigenesis. Accumulating evidence suggests that employing a quantitative trait locus mapping approach is effective in comprehending the genetic basis of promoter activity. By utilizing genotype data from The Cancer Genome Atlas and calculating corresponding promoter activity values using proActiv, we systematically evaluated the impact of genetic variants on promoter activity and identified >1.0 million promoter activity quantitative trait loci (paQTLs) as both cis- and trans-acting. Additionally, leveraging data from the genome-wide association study (GWAS) catalog, we discovered >1.3 million paQTLs that overlap with known GWAS linkage disequilibrium regions. Remarkably, ∼9324 paQTLs exhibited significant associations with patient prognosis. Moreover, investigating the impact of promoter activity on >1000 imputed antitumor therapy responses among pan-cancer patients revealed >43 000 million significant associations. Furthermore, ∼25 000 significant associations were identified between promoter activity and immune cell abundance. Finally, a user-friendly data portal, Pancan-paQTL (https://www.hbpding.com/PancanPaQTL/), was constructed for users to browse, search and download data of interest. Pancan-paQTL serves as a comprehensive multidimensional database, enabling functional and clinical investigations into genetic variants associated with promoter activity, drug responses and immune infiltration across multiple cancer types.