Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading causeof cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advancedcolorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predictingresistance in such first-line application.
Methods: To explore the potential molecular biomarkers predicting theresistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAsin serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNAexpression was further validated in an independent population by reverse transcription and quantitative realtimePCR.
Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarrayanalysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validationin an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated inresistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a todiscriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when theAUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonicantigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquireddrug resistance.
Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOXchemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker forpredicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectalcancer patients.