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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/cancers13071637
Journal or Publication Title: Cancers
Volume: 13
Number: 7
Page Range: p. 1637
Date: 2021
Divisions: Liver Injury and Cancer
Liver Enzymes in Metabolism and Inflammation
Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.3390/cancers13071637
ISSN: 2072-6694
Date Deposited: 10 Jun 2021 05:54
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 exonic LoF variants were most often associated with uterine carcinoma and lung carcinoma. All four DPP4-like genes were overexpressed in liver tumors 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 important for survival and that the DPP4 protease family, particularly DPP9, is important in the pathogenesis of human HCC.

Creators:
Creators
Email
Huang, Jiali Carrie
UNSPECIFIED
Emran, Abdullah Al
UNSPECIFIED
Endaya, Justine Moreno
UNSPECIFIED
McCaughan, Geoffrey W.
UNSPECIFIED
Gorrell, Mark D.
UNSPECIFIED
Zhang, Hui Emma
UNSPECIFIED
Last Modified: 10 Jun 2021 05:54
URI: https://eprints.centenary.org.au/id/eprint/997

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