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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.
Affiliation
  • Gonzalez RD; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Small GW; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Green AJ; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Akhtari FS; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Motsinger-Reif AA; Department of Biological Sciences, North Carolina State University, Raleigh, NC 27606, USA.
  • Quintanilha JCF; Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27606, USA.
  • Havener TM; Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • Reif DM; Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • McLeod HL; Clinical Development, Foundation Medicine, Boston, MA 02115, USA.
  • Wiltshire T; Structural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pharmaceuticals (Basel) ; 16(5)2023 May 17.
Article in En | MEDLINE | ID: mdl-37242540
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.
Key words

Full text: 1 Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: Pharmaceuticals (Basel) Year: 2023 Type: Article Affiliation country: United States

Full text: 1 Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: Pharmaceuticals (Basel) Year: 2023 Type: Article Affiliation country: United States