The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes
ADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehe...
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doaj-b4352bdb4e964ec0b6f276a97ddb804f2020-11-25T03:59:06ZengMDPI AGCancers2072-66942020-11-01123369336910.3390/cancers12113369The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical OutcomesDong Gui Hu0Peter I. Mackenzie1Pramod C. Nair2Ross A. McKinnon3Robyn Meech4Department of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, AustraliaDepartment of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, AustraliaDepartment of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, AustraliaDepartment of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, AustraliaDepartment of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, AustraliaADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehensive analyses of pan-cancer datasets from the Cancer Genome Atlas (TCGA) revealed differential intratumoral expression profiles for ADME genes in 21 different cancer types. Most genes also showed high interindividual variability within cancer-specific patient cohorts. Using Kaplan-Meier plots and logrank tests, we showed that intratumoral expression levels of twenty of the thirty-two core ADME genes were associated with overall survival (OS) in these cancers. Of these genes, five showed significant association with unfavourable OS in three cancers, including SKCM (<i>ABCC2</i>, <i>GSTP1</i>), KIRC (<i>CYP2D6</i>, <i>CYP2E1</i>), PAAD (<i>UGT2B7</i>); sixteen showed significant associations with favourable OS in twelve cancers, including BLCA (<i>UGT2B15</i>), BRCA (<i>CYP2D6</i>), COAD (<i>NAT1</i>), HNSC (<i>ABCB1</i>), KIRC (<i>ABCG2</i>, <i>CYP3A4</i>, <i>SLC22A2</i>, <i>SLC22A6</i>), KIRP (<i>SLC22A2</i>), LIHC (<i>CYP2C19</i>, <i>CYP2C8</i>, <i>CYP2C9</i>, <i>CYP3A5</i>, <i>SLC22A1</i>), LUAD (<i>SLC15A2</i>), LUSC (<i>UGT1A1</i>), PAAD (<i>ABCB1</i>), SARC (<i>ABCB1</i>), and SKCM (<i>ABCB1, DYPD</i>). Overall, these data provide compelling evidence supporting ADME genes as prognostic biomarkers and potential therapeutic targets. We propose that intratumoral expression of ADME genes may impact cancer patient survival by multiple mechanisms that can include metabolizing/transporting anticancer drugs, activating anticancer drugs, and metabolizing/transporting a variety of endogenous molecules involved in metabolically fuelling cancer cells and/or controlling pro-growth signalling pathways.https://www.mdpi.com/2072-6694/12/11/3369cancerdrug absorptiondrug distributiondrug metabolismdrug excretionendobiotic metabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dong Gui Hu Peter I. Mackenzie Pramod C. Nair Ross A. McKinnon Robyn Meech |
spellingShingle |
Dong Gui Hu Peter I. Mackenzie Pramod C. Nair Ross A. McKinnon Robyn Meech The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes Cancers cancer drug absorption drug distribution drug metabolism drug excretion endobiotic metabolism |
author_facet |
Dong Gui Hu Peter I. Mackenzie Pramod C. Nair Ross A. McKinnon Robyn Meech |
author_sort |
Dong Gui Hu |
title |
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes |
title_short |
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes |
title_full |
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes |
title_fullStr |
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes |
title_full_unstemmed |
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes |
title_sort |
expression profiles of adme genes in human cancers and their associations with clinical outcomes |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-11-01 |
description |
ADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehensive analyses of pan-cancer datasets from the Cancer Genome Atlas (TCGA) revealed differential intratumoral expression profiles for ADME genes in 21 different cancer types. Most genes also showed high interindividual variability within cancer-specific patient cohorts. Using Kaplan-Meier plots and logrank tests, we showed that intratumoral expression levels of twenty of the thirty-two core ADME genes were associated with overall survival (OS) in these cancers. Of these genes, five showed significant association with unfavourable OS in three cancers, including SKCM (<i>ABCC2</i>, <i>GSTP1</i>), KIRC (<i>CYP2D6</i>, <i>CYP2E1</i>), PAAD (<i>UGT2B7</i>); sixteen showed significant associations with favourable OS in twelve cancers, including BLCA (<i>UGT2B15</i>), BRCA (<i>CYP2D6</i>), COAD (<i>NAT1</i>), HNSC (<i>ABCB1</i>), KIRC (<i>ABCG2</i>, <i>CYP3A4</i>, <i>SLC22A2</i>, <i>SLC22A6</i>), KIRP (<i>SLC22A2</i>), LIHC (<i>CYP2C19</i>, <i>CYP2C8</i>, <i>CYP2C9</i>, <i>CYP3A5</i>, <i>SLC22A1</i>), LUAD (<i>SLC15A2</i>), LUSC (<i>UGT1A1</i>), PAAD (<i>ABCB1</i>), SARC (<i>ABCB1</i>), and SKCM (<i>ABCB1, DYPD</i>). Overall, these data provide compelling evidence supporting ADME genes as prognostic biomarkers and potential therapeutic targets. We propose that intratumoral expression of ADME genes may impact cancer patient survival by multiple mechanisms that can include metabolizing/transporting anticancer drugs, activating anticancer drugs, and metabolizing/transporting a variety of endogenous molecules involved in metabolically fuelling cancer cells and/or controlling pro-growth signalling pathways. |
topic |
cancer drug absorption drug distribution drug metabolism drug excretion endobiotic metabolism |
url |
https://www.mdpi.com/2072-6694/12/11/3369 |
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