| Objective:To find the single-nucleotide polymorphisms which relative with response to neoadjuvant chemotherapy in patients with cervical cancer, and provide useful inform to improve treatment selection, we performed a genome-wide association study in the Chinese Han population.Methods:We detected the genotype of SNPs in a total of231DNA samples from patients who received neoadjuvant chemotherapy. After the principal component analysis, a total of226patients (66nonresponders and160responders) were included in the genome-wide association study analysis. The SNPs with no correlation and smallest P value were validated in two independent follow-up stages. Follow-up1(multi-center validation), which included59non-responders and176responders, and Follow-up2(single-center validation), which included20non-responders and115responders.Results:A total of596patients were enrolled in this study, which include three stages. The chip discovery stage, the Follow-up1, and the Follow-up2stage include226patients,235patients,135patients respectively. After the three stage of analysis, we finally identified one SNP07(chromosome4, per allele OR=2.37, P=9.00×109) showed significant evidence of association with response to neoadjuvant chemotherapy. Another three SNPs showed strong association with response to neoadjuvant chemotherapy, SNP18(chromosome14, per allele OR=0.52, P=7.11×10-6), SNP20(chromosome16, per allele OR=1.98, P=3.15×10-6), and SNP13(chromosome10, per allele OR=0.48, P=1.59×10-5). When a score system was built by revalue the OR value, and add the scores of the four SNPs. We found the ratio of patients were not response to neoadjuvant chemotherapy increased with the total score increased. The non-response rate was57.6%with total score of13, and the non-response rate was only4.8%when the total score was6, which was the lowest total score.Conclusion:There were genetic factors which were associated with response to neoadjuvant chemotherapy in patients with cervical cancer. This finding may provide the new ideas in the study of effective of chemotherapy drugs, and instruct the clinical treatment. Objective:Neoadjuvant chemotherapy (NACT) could affect the levels of squamous cell carcinoma antigen (SCC-Ag). This study evaluates the predictive value of pre-and posttreatment SCC-Ag levels in patients with cervical cancer who were treated with NACT followed by radical surgery.Methods:A total of286patients with Stage IB1-ⅢB squamous cell carcinoma of the uterine cervix who were treated with NACT followed by radical hysterectomy were analyzed retrospectively. The relationship between SCC-Ag levels, the clinicopathologic parameters, the response to NACT and the three-year survival rate was investigated.Results:The levels of SCC-Ag were elevated (>3.5ng/mL) in43.8%of patients before NACT, and13.0%of patients after NACT. Pre-and posttreatment levels of SCC-Ag correlated with the response to NACT (P=0.010, and P<0.001), deep stromal infiltration (P=0.041, and P=0.006), and lymph node status (P<0.001, and P<0.001). In the multivariate analysis, the elevated pretreatment level of SCC-Ag was demonstrated to be an independent risk factor for Lymph node metastases (P<0.001). Patients with both pre-and posttreatment SCC-Ag levels≤3.5ng/mL showed the best3-year disease-free survival (DFS) and3-year overall survival (OS) compared with patients with either pre-or posttreatment levels>3.5ng/mL (P<0.001, and P<0.001, respectively). A multivariate analysis showed that posttreatment SCC-Ag levels were a strong independent predictor of OS (P=0.001) and DFS (P=0.012).Conclusion:Elevated pretreatment levels of SCC-Ag (>3.5ng/mL) indicated a poor response to NACT and a higher risk of lymph node metastases. Elevated posttreatment levels of SCC-Ag were correlated with poor DFS and OS. |
