DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma.

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in and loss of function (LoF) variants have not been explored. Human genomic databases, including The Cancer Genome Atlas (TCGA), were interrogated to identify LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that and are intolerant to LoF variants. exonic LoF variants were most often associated with uterine carcinoma and lung carcinoma. All four -like genes were overexpressed in liver tumors and their joint high expression was associated with poor survival in HCC. Increased expression was associated with obesity in HCC patients. High expression of genes that positively correlated with overexpression of , , and were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is important for survival and that the DPP4 protease family, particularly DPP9, is important in the pathogenesis of human HCC.