Effect of ABC transporter expression and mutational status on survival rates of cancer patients
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Onat Kadioglu
- Mohamed EM Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000582699600091&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.biopha.2020.110718
- eISSN
- 1950-6007
- Externe Identifier
- Clarivate Analytics Document Solution ID: OH6KI
- PubMed Identifier: 32932043
- ISSN
- 0753-3322
- Zeitschrift
- BIOMEDICINE & PHARMACOTHERAPY
- Schlüsselwörter
- ABC transporters
- Cancer
- Multidrug resistance
- P-glycoprotein
- Prognostic factor
- Survival analysis
- Artikelnummer
- ARTN 110718
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- Effect of ABC transporter expression and mutational status on survival rates of cancer patients
- Sub types
- Article
- Ausgabe der Zeitschrift
- 131
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Onat Kadioglu
- Mohamed EM Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.1016/j.biopha.2020.110718
- ISSN
- 0753-3322
- Zeitschrift
- Biomedicine & Pharmacotherapy
- Sprache
- en
- Artikelnummer
- 110718
- Paginierung
- 110718 - 110718
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.biopha.2020.110718
- Datum der Datenerfassung
- 2022
- Titel
- Effect of ABC transporter expression and mutational status on survival rates of cancer patients
- Ausgabe der Zeitschrift
- 131
Data source: Crossref
- Abstract
- ATP-binding cassette (ABC) transporters mediate multidrug resistance in cancer. In contrast to DNA single nucleotide polymorphisms in normal tissues, the role of mutations in tumors is unknown. Furthermore, the significance of their expression for prediction of chemoresistance and survival prognosis is still under debate. We investigated 18 tumors by RNA-sequencing. The mutation rate varied from 27,507 to 300885. In ABCB1, three hotspots with novel mutations were in transmembrane domains 3, 8, and 9. We also mined the cBioPortal database with 11,814 patients from 23 different tumor entities. We performed Kaplan-Meier survival analyses to investigate the effect of ABC transporter expression on survival rates of cancer patients. Novel mutations were also found in ABCA2, ABCA3, ABCB2, ABCB5, ABCC1-6, and ABCG2. Mining the cBioPortal database with 11,814 patients from 23 different tumor entities validated our results. Missense and in-frame mutations led to altered binding of anticancer drugs in molecular docking approaches. The ABCB1 nonsense mutation Q856* led to a truncated P-glycoprotein, which may sensitize tumors to anticancer drugs. The search for ABC transporter nonsense mutations represents a novel approach for precision medicine.. Low ABCB1 mRNA expression correlated with significantly longer survival in ovarian or kidney cancer and thymoma. In cancers of breast, kidney or lung, ABC transporter expression correlated with different tumor stages and human populations as further parameters to refine strategies for more individualized chemotherapy.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Onat Kadioglu
- Mohamed EM Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- DOI
- 10.1016/j.biopha.2020.110718
- eISSN
- 1950-6007
- Externe Identifier
- PubMed Identifier: 32932043
- Funding acknowledgements
- Johannes Gutenberg University, Mainz, Germany:
- Open access
- false
- ISSN
- 0753-3322
- Zeitschrift
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Schlüsselwörter
- Humans
- Neoplasms
- ATP-Binding Cassette Transporters
- Survival Rate
- Sequence Analysis, RNA
- Mutation
- Polymorphism, Single Nucleotide
- Adult
- Aged
- Aged, 80 and over
- Middle Aged
- Female
- Male
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2020
- Paginierung
- 110718
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2020
- Titel
- Effect of ABC transporter expression and mutational status on survival rates of cancer patients.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 131
Data source: Europe PubMed Central
- Abstract
- ATP-binding cassette (ABC) transporters mediate multidrug resistance in cancer. In contrast to DNA single nucleotide polymorphisms in normal tissues, the role of mutations in tumors is unknown. Furthermore, the significance of their expression for prediction of chemoresistance and survival prognosis is still under debate. We investigated 18 tumors by RNA-sequencing. The mutation rate varied from 27,507 to 300885. In ABCB1, three hotspots with novel mutations were in transmembrane domains 3, 8, and 9. We also mined the cBioPortal database with 11,814 patients from 23 different tumor entities. We performed Kaplan-Meier survival analyses to investigate the effect of ABC transporter expression on survival rates of cancer patients. Novel mutations were also found in ABCA2, ABCA3, ABCB2, ABCB5, ABCC1-6, and ABCG2. Mining the cBioPortal database with 11,814 patients from 23 different tumor entities validated our results. Missense and in-frame mutations led to altered binding of anticancer drugs in molecular docking approaches. The ABCB1 nonsense mutation Q856* led to a truncated P-glycoprotein, which may sensitize tumors to anticancer drugs. The search for ABC transporter nonsense mutations represents a novel approach for precision medicine.. Low ABCB1 mRNA expression correlated with significantly longer survival in ovarian or kidney cancer and thymoma. In cancers of breast, kidney or lung, ABC transporter expression correlated with different tumor stages and human populations as further parameters to refine strategies for more individualized chemotherapy.
- Date of acceptance
- 2020
- Autoren
- Onat Kadioglu
- Mohamed EM Saeed
- Markus Munder
- Andreas Spuller
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/32932043
- DOI
- 10.1016/j.biopha.2020.110718
- eISSN
- 1950-6007
- Zeitschrift
- Biomed Pharmacother
- Schlüsselwörter
- ABC transporters
- Cancer
- Multidrug resistance
- P-glycoprotein
- Prognostic factor
- Survival analysis
- ATP-Binding Cassette Transporters
- Adult
- Aged
- Aged, 80 and over
- Female
- Humans
- Male
- Middle Aged
- Molecular Docking Simulation
- Mutation
- Neoplasms
- Polymorphism, Single Nucleotide
- Sequence Analysis, RNA
- Survival Rate
- Sprache
- eng
- Country
- France
- Paginierung
- 110718
- PII
- S0753-3322(20)30911-2
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- Effect of ABC transporter expression and mutational status on survival rates of cancer patients.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 131
Data source: PubMed
- Beziehungen:
- Property of