| Summary: | 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 <i>UGT</i> 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 <i>UGT</i> genes (COAD, KIRC, KIRP, LIHC, PAAD); six <i>UGT</i> genes (<i>1A6</i>, <i>1A9</i>, <i>1A10</i>, <i>2A3</i>, <i>2B7</i>, <i>UGT8</i>) showed high expression in five or more different cancers. Kaplan–Meier plots and logrank tests revealed that six <i>UGT</i> genes were significantly associated with increased overall survival (OS) rates [<i>UGT1A1</i> (LUSC), <i>UGT1A6</i> (ACC), <i>UGT1A7</i> (ACC), <i>UGT2A3</i> (KIRC), <i>UGT2B15</i> (BLCA, SKCM)] or decreased OS rates [<i>UGT2B15</i> (LGG), <i>UGT8</i> (UVM)] in specific cancers. Finally, differential expression analysis of 611 patients from 12 TCGA cancers identified 16 <i>UGT</i> genes (<i>1A1</i>, <i>1A3</i>, <i>1A6</i>, <i>1A7</i>, <i>1A8</i>, <i>1A9</i>, <i>1A10</i>, <i>2A1</i>, <i>2A3</i>, <i>2B4</i>, <i>2B7</i>, <i>2B11</i>, <i>2B15</i>, <i>3A1</i>, <i>3A2</i>, <i>UGT8</i>) that were up/downregulated in at least one cancer relative to normal tissues. In conclusion, our data show widespread expression of <i>UGT</i> genes in cancers, highlighting the capacity for intratumoural drug metabolism through the UGT conjugation pathway. The data also suggests the potentials for specific <i>UGT</i> genes to serve as prognostic biomarkers or therapeutic targets in cancers.
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