BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is a deadly disease with a poor prognosis. The single nucleotide polymorphisms (SNPs) involved in microRNA (miRNA) functions are potential biomarkers for prognosis of various human cancers. We investigated the association of the miRNA-related SNPs with the prognosis of ESCC. METHODS: A total of 504 patients with ESCC were enrolled. The genotypes of 18 miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the prognosis of patients randomly assigned to a training set (n = 129) or an independent replication set (n = 375). RESULTS: In the training group, only the rs4919510 SNP of the mir-608 gene was significantly associated with clinical outcome (CG vs. GG, hazard ratio [HR] 0.47, 95 % confidence interval [CI] 0.27-0.82, P = 0.008 for death, HR 0.47, 95 % CI 0.29-0.77, P = 0.002 for recurrence). The association for overall survival was confirmed in an independent replication group (CG vs. GG, HR 0.74, 95 % CI 0.56-0.97, P = 0.031 for death). Two other SNPs, rs14035 of RAN and rs7813 of GEMIN4, showed a borderline significant association with the prognosis of ESCC. In a combined analysis, we demonstrated the cumulative effect of the mir-608, RAN, and GEMIN4 polymorphisms on the clinical outcome of ESCC (HR 1.40, 95 % CI 1.18-1.67, P trend < 0.001 for mortality, HR 1.30, 95 % CI 1.10-1.53, P trend = 0.002 for recurrence). The cumulative effect was more evident in patients receiving concurrent chemoradiotherapy. CONCLUSIONS: The hereditary genetic polymorphisms of mir-608, RAN, and GEMIN4 can serve as predictors for clinical outcome in ESCC patients treated with concurrent chemoradiotherapy.
RCT Entities:
BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is a deadly disease with a poor prognosis. The single nucleotide polymorphisms (SNPs) involved in microRNA (miRNA) functions are potential biomarkers for prognosis of various humancancers. We investigated the association of the miRNA-related SNPs with the prognosis of ESCC. METHODS: A total of 504 patients with ESCC were enrolled. The genotypes of 18 miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the prognosis of patients randomly assigned to a training set (n = 129) or an independent replication set (n = 375). RESULTS: In the training group, only the rs4919510 SNP of the mir-608 gene was significantly associated with clinical outcome (CG vs. GG, hazard ratio [HR] 0.47, 95 % confidence interval [CI] 0.27-0.82, P = 0.008 for death, HR 0.47, 95 % CI 0.29-0.77, P = 0.002 for recurrence). The association for overall survival was confirmed in an independent replication group (CG vs. GG, HR 0.74, 95 % CI 0.56-0.97, P = 0.031 for death). Two other SNPs, rs14035 of RAN and rs7813 of GEMIN4, showed a borderline significant association with the prognosis of ESCC. In a combined analysis, we demonstrated the cumulative effect of the mir-608, RAN, and GEMIN4 polymorphisms on the clinical outcome of ESCC (HR 1.40, 95 % CI 1.18-1.67, P trend < 0.001 for mortality, HR 1.30, 95 % CI 1.10-1.53, P trend = 0.002 for recurrence). The cumulative effect was more evident in patients receiving concurrent chemoradiotherapy. CONCLUSIONS: The hereditary genetic polymorphisms of mir-608, RAN, and GEMIN4 can serve as predictors for clinical outcome in ESCC patients treated with concurrent chemoradiotherapy.
Authors: Mi Na Kim; Jung Oh Kim; Seung Min Lee; Hana Park; Ju Ho Lee; Kyu Sung Rim; Seong Gyu Hwang; Nam Keun Kim Journal: PLoS One Date: 2016-09-09 Impact factor: 3.240