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

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  • Gonzalez, Ricardo D.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Small, George W.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Green, Adrian J.
    • Other Affiliation: North Carolina State University
  • Akhtari, Farida S.
    • Other Affiliation: National Institute of Environmental Health Sciences
  • Motsinger-Reif, Alison A.
    • Other Affiliation: National Institute of Environmental Health Sciences
  • Quintanilha, Julia C. F.
    • Other Affiliation: Foundation Medicine
  • Havener, Tammy M.
    • Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
  • Reif, David M.
    • Other Affiliation: National Institute of Environmental Health Sciences
  • McLeod, Howard L.
    • Other Affiliation: Utah Tech University
  • Wiltshire, Tim
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
Abstract
  • 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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  • Article
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  • In Copyright
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  • Attribution 4.0 International
Journal title
  • Pharmaceuticals
Journal volume
  • 16
Journal issue
  • 5
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  • 757
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  • English
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  • 1424-8247
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  • MDPI

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