The Relationship Between The Level Of MicroRNA Expression And The Prognosis Of Esophageal Cancer In Patients With High Risk Of Esophageal Cancer

Objective:MicroRNAs have been shown to be associated with the prognosis of esophageal cancer,suggesting that miRNAs can play an important role in guiding decision-making.The aim of this study was to assess the prognostic potential of microRNA associated with zinc deficiency found in high incidence areas of esophageal cancer.Methods:1 MiRNAs associated with zinc deficiency were isolated from esophageal cancer cell lines cultured at different levels of zinc.2 We tried 4 levels of ZnSO4(25,50,75 and 100uM/L)for preliminary experiment and chose 50uM/L in this experiment.The expression levels of mi RNAs were determined for each cell line to analyse the effect that Zn levels had on the miRNAs.The miRNAs that were measured included mi R-21,miR-31,mi R-93,miR-193 a,miR-193 b,miR-342 and miR-375,and their relationships with Zn levels were determined using Target Scan Human.3 The expression levels of miRNAs were quantified using qRT-PCR.The potential prognostic value of selected miRNAs was assessed in a cohort study of 92 patients with high incidence of esophageal cancer in China.4 The correlation between miRNA and patient characteristics was assessed using the χ2 statistical test or the Fisher exactness method.The Cox risk proportional model was used to assess the correlation between miRNA and overall survival(OS).Results:1 The zinc levels of patients and control groups in serumThe serum zinc levels of patients and healthy volunteers from high incidence areas of EC were measured.The serum zinc level of EC patients was81.00±4.03ug/100mL;the serum zinc level of control from high incidence areas was 87.20±5.67ug/100 mL.We did a analysis and found that the serum zinc level of patients was lower than controls(P<0.001).2 Effects of Zn on miRNAs in EC cell linesWe compared the expression levels of miRNAs in human EC cell lines that were cultured with or without Zn.The expression levels of the miRNAs in the KYSE170 cells incubated without Zn were used as the standards and the relative levels of miR-21,mi R-31,miR-93,mi R-375,mi R-193 a,mi R-193 b,mi R-342 were 0.76(P<0.05),0.67(P<0.05),0.79(P<0.05),1.42(P<0.05),1.05,0.98,1.03;The expression levels of the miRNAs in the KYSE170 cells incubated without Zn were used as the standards,and the relative levels of mi R-21,miR-31,mi R-93,miR-375,miR-193 a,miR-193 b,miR-342 were0.80(P<0.05),0.54(P<0.05),0.62(P<0.05),1.38(P<0.05),1.07,1.15,0.97.3 Association of the miRNAs with patient characteristics and prognosticThe patients expressing high levels of miR-21 had poor OS(HR:2.15,95%CI:1.16-3.97),whereas those with high levels of miR-375 had improved OS(HR:0.47,95%CI:0.26-0.87).The patients with both a high level of mi R-375 and a low level of miR-21 had significantly better outcomes.Conclusions:MiR-21 and miR-375 can be used as prognostic biomarkers for esophageal cancer in high incidence areas,and the combination of these markers will have a better effect on the prognosis of esophageal cancer.