Investigation On The Relationship Of Circulating MiR-21to Response、Toxicity And Survival In Advanced Colorectal Cancer Patients Treated With Standard First-line Chemotherapy Regime

Objectives:miR-21has been recognized as an ‘‘onco-microRNA’’.The aim of this study wasto investigate miR-21expression in serum of colorectal cancer and its correlationwith chemotherapy effect of CRC patients. To investigate the relationship betweenmiR-21serum levels of advanced colorectal cancer and dynamic changes duringchemotherapy and acceptance of standard first-line chemotherapy, toxicity and theOS and PFS of patients.Methods:1. We collected serum and corresponding tumor tissue from nine pathologicallydiagnosed with colorectal cancer patients. The expression levels of miR21in serumand tissue were examined by real-time polymerase chain reaction (miR-423asreference gene). The bivariate correlation analysis was used to test the correlation ofmiR21levels between serum and tissue.2. Thirty seven cases of advanced colorectal cancer patients with standardfirst-line chemotherapy included in this study. The lesions baseline was established byCT scan. The lesion was observed again by CT scan, respectively beforechemotherapy and after chemotherapy. The serum miR-21expression levels beforeand after chemotherapy was examined by real-time polymerase chain reaction(miR-423as reference gene). The mean Δ Ct value of miR21in patients beforechemotherapy defined as the standard. Δ Ct value higher than the mean value definedas low expression, and instead defined as high expression. If Δ Ct value increased20%after chemotherapy compared to before chemotherapy defined as the decrease.Chemotherapy toxicity was recorded during chemotherapy and patients werefollowed up until death. Chi-square test was used to analysis the relationship betweenthe serum miR21levels and the pathological features of advanced colorectal cancer.3. The age, gender, ECOG score, histological grade, CA-199, CEA, LDH, HGB,PLT, short-term effect, the dynamic changes of serum miR-21before chemotherapy and after chemotherapy and other factors included in the Kaplan-Meier Survivalanalysis between the two groups were compared using Log-rank, for unilabiateanalysis showed statistically significant factors included COX regression analysis,using two-sided test, taking p <0.05as statistically significant.Results:1. The miR-21Δ Ct value in serum and corresponding tumor tissue which from9colorectal cancer patients was3.982±0.7549and17.616±0.3526respectively.Bivariate correlation analysis correlation coefficient was0.668(P=0.041). The resultsindicate that the serum miR-21levels closely associated with the miR21expressionlevels in tumor tissue.2. There are no statistical differences of hematologic, digestive tract and nervoussystem toxicity between patients with different serum miR-21levels. However,patients with different circulating miR-21levels showed different tumor grade, CEAlevels and chemotherapy effect.3. The mPFS and mOS value of37cases of patients with advanced colorectalcancer was8.837months and19.6months, respectively. Before treatment, there were20patients with low miR-21expression and17patients with high miR-21expression.The mPFS were9.4+/-1.6months (95%CI5.3to9.6) vs6.8+/-2.7months (95%CI8.5to9.4). The difference was statistically significant (p=0.019).Serum miR-21levelsdecreased in17patients and increased in20patients after chemotherapy compared tothe serum miR-21levels in patients before treatment. The mPFS were9.5+/-0.29months (95%CI8.9~10) vs7.5+/-0.67months (95%CI6.1to8.8). The difference wasstatistically significant (p=0.35).COX multiple factors regression analysis indicatethat ECOG score, tumor differentiation degree, LDH level, the curative effect ofchemotherapy, miR-21dynamic changes in expression level is the independentprognostic factors that affects the mPFS.20patients serum miR-21and17patientswith low expression of serum miR-21patients with high expression of mOS were23.5+/-0.89months (95%CI22.7to26.3) vs17.5+/-1.85months (95%CI13.9to21.2), the difference was statistically significant (P=0.001). COX multiple factorsregression analysis showed the ECOG score, curative effect of chemotherapy,chemotherapy before miR-21expression level and serum miR-21dynamic changes in expression level is the independent prognostic factors of mOS.Conclusion:1. Serum miR-21levels have certain correlation with tumor tissue miR–21expression levels;2. Serum miR-21levels before chemotherapy have no correlation with thechemotherapy toxitiy of advanced colorectal cancer patients; Patients with higherserum miR-21levels reveal worse chemotherapy effect than patients with lowerserum miR-21levels.3. The serum miR-21is expected to replace tissue miR-21to predict the efficacyand prognosis of colorectal cancer chemotherapy.