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MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients

Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene MKX-AS1 and partnered sense gene MKX could impact the response of genetically varied cell lines to OXAL...

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Autores principales: Gonzalez, Ricardo D., Small, George W., Green, Adrian J., Akhtari, Farida S., Motsinger-Reif, Alison A., Quintanilha, Julia C. F., Havener, Tammy M., Reif, David M., McLeod, Howard L., Wiltshire, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222429/
https://www.ncbi.nlm.nih.gov/pubmed/37242540
http://dx.doi.org/10.3390/ph16050757
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author Gonzalez, Ricardo D.
Small, George W.
Green, Adrian J.
Akhtari, Farida S.
Motsinger-Reif, Alison A.
Quintanilha, Julia C. F.
Havener, Tammy M.
Reif, David M.
McLeod, Howard L.
Wiltshire, Tim
author_facet Gonzalez, Ricardo D.
Small, George W.
Green, Adrian J.
Akhtari, Farida S.
Motsinger-Reif, Alison A.
Quintanilha, Julia C. F.
Havener, Tammy M.
Reif, David M.
McLeod, Howard L.
Wiltshire, Tim
author_sort Gonzalez, Ricardo D.
collection PubMed
description Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene MKX-AS1 and partnered sense gene MKX could impact the response of genetically varied cell lines to OXAL treatment. This study found that the expression levels of MKX-AS1 and MKX in lymphocytes (LCLs) and CRC cell lines differed between the rs11006706 genotypes, indicating that this gene pair could play a role in OXAL response. Further analysis of patient survival data from the Cancer Genome Atlas (TCGA) and other sources showed that patients with high MKX-AS1 expression status had significantly worse overall survival (HR = 3.2; 95%CI = (1.17–9); p = 0.024) compared to cases with low MKX-AS1 expression status. Alternatively, high MKX expression status had significantly better overall survival (HR = 0.22; 95%CI = (0.07–0.7); p = 0.01) compared to cases with low MKX expression status. These results suggest an association between MKX-AS1 and MKX expression status that could be useful as a prognostic marker of response to OXAL and potential patient outcomes in CRC.
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spelling pubmed-102224292023-05-28 MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients Gonzalez, Ricardo D. Small, George W. Green, Adrian J. Akhtari, Farida S. Motsinger-Reif, Alison A. Quintanilha, Julia C. F. Havener, Tammy M. Reif, David M. McLeod, Howard L. Wiltshire, Tim Pharmaceuticals (Basel) Article Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene MKX-AS1 and partnered sense gene MKX could impact the response of genetically varied cell lines to OXAL treatment. This study found that the expression levels of MKX-AS1 and MKX in lymphocytes (LCLs) and CRC cell lines differed between the rs11006706 genotypes, indicating that this gene pair could play a role in OXAL response. Further analysis of patient survival data from the Cancer Genome Atlas (TCGA) and other sources showed that patients with high MKX-AS1 expression status had significantly worse overall survival (HR = 3.2; 95%CI = (1.17–9); p = 0.024) compared to cases with low MKX-AS1 expression status. Alternatively, high MKX expression status had significantly better overall survival (HR = 0.22; 95%CI = (0.07–0.7); p = 0.01) compared to cases with low MKX expression status. These results suggest an association between MKX-AS1 and MKX expression status that could be useful as a prognostic marker of response to OXAL and potential patient outcomes in CRC. MDPI 2023-05-17 /pmc/articles/PMC10222429/ /pubmed/37242540 http://dx.doi.org/10.3390/ph16050757 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gonzalez, Ricardo D.
Small, George W.
Green, Adrian J.
Akhtari, Farida S.
Motsinger-Reif, Alison A.
Quintanilha, Julia C. F.
Havener, Tammy M.
Reif, David M.
McLeod, Howard L.
Wiltshire, Tim
MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title_full MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title_fullStr MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title_full_unstemmed MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title_short MKX-AS1 Gene Expression Associated with Variation in Drug Response to Oxaliplatin and Clinical Outcomes in Colorectal Cancer Patients
title_sort mkx-as1 gene expression associated with variation in drug response to oxaliplatin and clinical outcomes in colorectal cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222429/
https://www.ncbi.nlm.nih.gov/pubmed/37242540
http://dx.doi.org/10.3390/ph16050757
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