Abstract
Abstract Background: 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 outcomes. Methods: At discovery stage, we profiled 1075 cfmiRNAs in 6 pooled serum samples from 30 EA patients and 30 cancer-free control subjects. After filtration, a total of 589 cfmiRNAs were stably detectable in the serum samples. The most significantly differential expressed cfmiRNAs were then validated the association with overall survival (OS) in an independent cohort of 82 patients, using Log-Rank test and multivariate Cox regression models in overall samples or stratified by HP infection status. qRT-PCR was used for cfmiRNA profiling in validation. HP infection status was determined by immunoblotting assay. Results: We identified a 21-cfmiRNA panel that could distinguish EA patients from cancer-free subjects (multiple response analysis by Hotelling T test, P = 3.0E-12). In validation, the OS analysis among HP-positive subtype patients showed that no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 9 cfmiRNAs were significantly associated with OS (minimal P = 1.9E-4, all FDR adjusted q-value < 0.05). A risk-score analysis by combining the 9 cfmiRNA biomarkers showed a worse outcome in high-risk group (HR = 12.82, P = 0.0075) that showed better prediction of prognosis than individual cfmiRNA alone. Conclusions: Our findings suggest that deregulated cfmiRNAs may contribute to EA prognosis and HP infection status may modify the association between cfmiRNAs and EA survival. Citation Format: Yongyue Wei, Li Su, David C. Christiani. Whole-genome microRNA profiling identifies prognostic serum biomarkers of esophageal adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4014. doi:10.1158/1538-7445.AM2015-4014
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