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DPP9: Comprehensive In Silico Analyses of Loss of Function Gene Variants and Associated Gene Expression Signatures in Human Hepatocellular Carcinoma.
Huang, Jiali Carrie; Emran, Abdullah Al; Endaya, Justine Moreno; McCaughan, Geoffrey W; Gorrell, Mark D; Zhang, Hui Emma.
  • Huang JC; Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • Emran AA; Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • Endaya JM; Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • McCaughan GW; Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
  • Gorrell MD; AW Morrow GE & Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
  • Zhang HE; Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Cancers (Basel) ; 13(7)2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1295765
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Reviews Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Cancers13071637

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Reviews Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Cancers13071637