Forkhead Box Q1 Expression Is Associated With Tumor Location of Right-Sided Colon, But Not With Acquisition of Oxaliplatin Resistance in Colorectal Cancer

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 OHP-resistant clones derived from HCT116, but not DLD1 were also resistant against the other drugs used for CRC treatment (5-fluorouracil, OHP, and trifluorothymidine) and their xenograft tumors were resistant against OHP treatment. Among the candidate genes derived from microarray analysis using the samples of OHP-resistant cells and their xenografts derived from HCT116, Forkhead box Q1 (FOXQ1) was further assessed for validation of OHP resistance and its association with clinicopathological features. Modification of FOXQ1 via siRNA knockdown and expression vector could not confirm the involvement of FOXQ1 in OHP resistance. In 173 CRC patients, FOXQ1 was upregulated in most CRC tumors compared to normal colonic mucosa. FOXQ1 expression was significantly different by tumor location of the right-sided colon cancer compared with left-sided and rectal cancer. Moreover, expression level was significantly associated with prognosis in advanced and recurrent patients. TCGA data also showed significant association of FOXQ1 expression with tumor location. Our results indicated that FOXQ1 expression is associated with tumor location of right-sided colon, but not with acquisition of OHP resistance in colorectal cancer.