Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of H. pylori infection status.

[esophageal adenocarcinoma]

Cell free circulating microRNAs (cfmiRNAs ) have been recognized as robust and stable biomarkers of cancers . However , little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA ). In this study , we explored whether specific cfmiRNA profiles could predict EA prognosis and whether H . pylori (HP ) infection status could influence the association between cfmiRNAs and EA survival outcome . We profiled 1075 miRNAs in pooled serum samples from 30 EA patients and 30 healthy controls . The most relevant cfmiRNAs were then assessed for their associations with EA survival in an independent cohort of 82 patients , using Log-rank test and multivariate Cox regression models . qRT-PCR was used for cfmiRNA profiling . HP infection status was determined by immunoblotting assay . We identified a panel of eighteen cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3 .0 E -12 ). In overall analysis and in HP -positive subtype patients , no cfmiRNA was significantly associated with EA prognosis . In HP -negative patients , however , 15 cfmiRNAs were significantly associated with overall survival (OS ) (all P < 0 .05 ). A combined 2 -cfmiRNA (low miR-3935 and high miR-4286 ) risk score was constructed that showed greater risk for worse OS (HR = 2 .22 , P = 0 .0019 ) than individual cfmiRNA alone . Patients with high -risk score had >10 -fold increased risk of death than patients with low risk score (P = 0 .0302 ; HR = 10 .91 , P = 0 .0094 ). Our findings suggest that dysregulated cfmiRNAs may contribute to EA survival outcome and HP infection status may modify the association between cfmiRNAs and EA survival .