FOXQ1 expression in colorectal cancer is associated with tumor location

Abstract Oxaliplatin (OHP) is a reagent for the standard treatment of advanced and recurrent colorectal cancer (CRC), although OHP resistance mechanisms are not fully elucidated. We found that HCT116-derived OHP-resistant clones (HCT/OHPs), but not DLD1-derived OHP-resistant clones also were resistant to the other drugs used for CRC treatment (5-fluorouracil, irinotecan, and trifluorothymidine), and HCT/OHP-derived tumors were resistant to OHP treatment. Among the candidate genes derived from microarray analysis using the samples of HCT/OHP cells and HCT/OHP-derived tumors, Forkhead box Q1 (FOXQ1) was further assessed to validate OHP resistance and its association with clinicopathological features. In our 173 cohort and 587 TCGA samples, FOXQ1 was upregulated in most CRC tumors compared to normal colonic mucosa and associated with tumor location of the right-sided colon and KRAS/BRAF mutation status. Possible association with prognosis in advanced CRC in our cohort and with microsatellite instability and advanced stage in TCGA samples were indicated. Modification of FOXQ1 via siRNA knockdown and expression vector could not confirm the involvement of FOXQ1 in OHP resistance. In conclusion, our results indicates that FOXQ1 is upregulated in CRC and FOX1 expression is associated with tumor location and KRAS/BRAF mutation status, but is not involved in the OHP resistance mechanism.