Huang Jiali Carrie, Emran Abdullah Al, Endaya Justine Moreno, McCaughan Geoffrey W, Gorrell Mark D, Zhang Hui Emma
Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
AW Morrow GE & Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
Cancers (Basel). 2021 Apr 1;13(7):1637. doi: 10.3390/cancers13071637.
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.
二肽基肽酶（DPP）9、DPP8、DPP4和成纤维细胞活化蛋白（FAP）是S9b蛋白酶家族的四个具有酶活性的成员。尚未探究DPP9与人类肝癌的关联、其外显子单核苷酸多态性（SNP）以及功能丧失（LoF）变体。我们查询了包括癌症基因组图谱（TCGA）在内的人类基因组数据库，以识别LoF变体和相关癌症。对肝细胞癌（HCC）数据进行了生存和基因特征分析。我们发现 和 对LoF变体不耐受。 的外显子LoF变体最常与子宫癌和肺癌相关。所有四个类 基因在肝肿瘤中均过度表达，它们的联合高表达与HCC患者的不良生存相关。 表达增加与HCC患者肥胖相关。与 、 和 过度表达呈正相关的基因的高表达与HCC患者的极差生存相关。这些正相关基因的富集通路分析显示了Toll样受体和SUMO化通路。这种全面的数据挖掘表明DPP9对生存很重要，并且DPP4蛋白酶家族，尤其是DPP9，在人类HCC的发病机制中很重要。
