Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Associations Between DPP9 Expression, Survival and Gene Expression Signature in Human Hepatocellular Carcinoma: Comprehensive In Silico Analyses

Version 1 : Received: 11 January 2021 / Approved: 13 January 2021 / Online: 13 January 2021 (12:13:37 CET)

A peer-reviewed article of this Preprint also exists.

Jiali Carrie Huang, Abdullah Al Emran, Justine Moreno Endaya, Geoffrey W McCaughan, Mark D Gorrell, Hui Emma Zhang 2021 DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma. Cancers, 13(7):1637. Jiali Carrie Huang, Abdullah Al Emran, Justine Moreno Endaya, Geoffrey W McCaughan, Mark D Gorrell, Hui Emma Zhang 2021 DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma. Cancers, 13(7):1637.

Journal reference: Cancers 2021, 13, 1637
DOI: 10.3390/cancers13071637

Abstract

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 DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 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 essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

Keywords

DPP9; SNPs; Hepatocellular carcinoma; Survival; TCGA; DPP4 gene family

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