The Expression Profiles and Deregulation of UDP-Glycosyltransferase () Genes in Human Cancers and Their Association with Clinical Outcomes

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Sep 10

PMID 34503303

Citations 11

Authors

Dong Gui Hu

Shashikanth Marri

Peter I Mackenzie

Julie-Ann Hulin

Ross A McKinnon

Robyn Meech

Affiliations

Soon will be listed here.

Abstract

The human UDP-glycosyltransferase (UGTs) superfamily has 22 functional enzymes that play a critical role in the metabolism of small lipophilic compounds, including carcinogens, drugs, steroids, lipids, fatty acids, and bile acids. The expression profiles of genes in human cancers and their impact on cancer patient survival remains to be systematically investigated. In the present study, a comprehensive analysis of the RNAseq and clinical datasets of 9514 patients from 33 different TCGA (the Genome Cancer Atlas) cancers demonstrated cancer-specific UGT expression profiles with high interindividual variability among and within individual cancers. Notably, cancers derived from drug metabolizing tissues (liver, kidney, gut, pancreas) expressed the largest number of genes (COAD, KIRC, KIRP, LIHC, PAAD); six genes (, , , , , ) showed high expression in five or more different cancers. Kaplan-Meier plots and logrank tests revealed that six genes were significantly associated with increased overall survival (OS) rates [ (LUSC), (ACC), (ACC), (KIRC), (BLCA, SKCM)] or decreased OS rates [ (LGG), (UVM)] in specific cancers. Finally, differential expression analysis of 611 patients from 12 TCGA cancers identified 16 genes (, , , , , , , , , , , , , , , ) that were up/downregulated in at least one cancer relative to normal tissues. In conclusion, our data show widespread expression of genes in cancers, highlighting the capacity for intratumoural drug metabolism through the UGT conjugation pathway. The data also suggests the potentials for specific genes to serve as prognostic biomarkers or therapeutic targets in cancers.

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