The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes
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 canc...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4491 |
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| author | Dong Gui Hu Shashikanth Marri Peter I. Mackenzie Julie-Ann Hulin Ross A. McKinnon Robyn Meech |
| author_facet | Dong Gui Hu Shashikanth Marri Peter I. Mackenzie Julie-Ann Hulin Ross A. McKinnon Robyn Meech |
| author_sort | Dong Gui Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T08:15:09Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:15:09Z |
| publishDate | 2021-09-01 |
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| series | Cancers |
| spelling | doaj.art-ebb7c20109024dc6b923b2feb742ab252023-11-22T10:28:15ZengMDPI AGCancers2072-66942021-09-011317449110.3390/cancers13174491The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical OutcomesDong Gui Hu0Shashikanth Marri1Peter I. Mackenzie2Julie-Ann Hulin3Ross A. McKinnon4Robyn Meech5Dicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaDicipline of Molecular Medicine and Pathology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaDicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaDicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaDicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaDicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaThe 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.https://www.mdpi.com/2072-6694/13/17/4491UDP-glycosyltransferaseUDP-glucuronosyltransferasecancerdrug metabolismgene expressiondifferential gene expression |
| spellingShingle | Dong Gui Hu Shashikanth Marri Peter I. Mackenzie Julie-Ann Hulin Ross A. McKinnon Robyn Meech The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes Cancers UDP-glycosyltransferase UDP-glucuronosyltransferase cancer drug metabolism gene expression differential gene expression |
| title | The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes |
| title_full | The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes |
| title_fullStr | The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes |
| title_full_unstemmed | The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes |
| title_short | The Expression Profiles and Deregulation of UDP-Glycosyltransferase (<i>UGT</i>) Genes in Human Cancers and Their Association with Clinical Outcomes |
| title_sort | expression profiles and deregulation of udp glycosyltransferase i ugt i genes in human cancers and their association with clinical outcomes |
| topic | UDP-glycosyltransferase UDP-glucuronosyltransferase cancer drug metabolism gene expression differential gene expression |
| url | https://www.mdpi.com/2072-6694/13/17/4491 |
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