Abstract 2915: Circulating miRNAs as potential biomarkers for esophageal adenocarcinoma risk and clinical outcomes

Abstract

Abstract Esophageal adenocarcinoma (EAC) is a deadly disease with increased incidence in Western countries. More than half of EAC patients are diagnosed at an advanced stage, when curative surgery is not an option. Platinum- and fluorouracil (FU)-based chemo-radiation are the mainstay of treatments for advanced EAC with modest survival benefit but substantial toxicity. The lack of effective early detection tool and the low rate of treatment responses for advanced disease result in a dismal overall 5-year survival rate of <15%. Identification of minimally invasive, blood-based biomarkers for early diagnosis and prognosis/therapy response is essential to improve the overall outcome for EAC patients. In this study, we aimed to identify serum miRNAs as diagnostic and/or prognosis/predictive biomarkers for EAC. Firstly, a global screening of human miRNAs was conducted using TaqMan Human MicroRNA Microarray (754 miRNAs) in a pilot study. We selected 89 stably detectable miRNAs and measured their expression in 349 serum samples (165 cases vs184 controls) from Caucasian population using a newly designed Fluidigm BioMark™ customized panel. After quality control, 77 miRNAs were included in the final analysis. Five miRNAs (miR-126, miR-142-3p, miR-331-3p, miR-18a and miR-18) were significantly differentially-expressed between cases and controls (P<0.05). Among the 165 EAC patients, five miRNAs were significantly associated with survival and two with recurrence (P<0.05). Interestingly, higher miR-30c level was significantly associated with decreased risk for both death (HR=0.28, 95%CI= 0.12- 0.65, P= 0.003) and recurrence (HR= 0.49, 95%CI= 0.24- 0.99, P= 0.047). Among 118 patients received chemo/chemoradiation, 93% and 84% have received 5FU or platinum-agent, respectively. MiR-142-3p was associated with an increased risk of recurrence in the platinum-based subgroup (HR=2.67, 95%CI= 1.09- 6.56, P=0.032). Higher levels of miR-30c was associated with decreased risk of death in both treatment subgroups with a similar effect. MiR-26a was significantly associated with an increased risk of death (HR=5.78, 95%CI= 1.59-21.06, P=0.008) and recurrence (HR=7.76, 95%CI= 2.30-26.18, P=0.001) in the platinum subgroup, whereas miR-127-3p and miR-486-5p were significantly associated with both survival and recurrence in the 5FU subgroup. We further tested the expression of candidate serum miRNAs in tissue samples (15 normal and 81 tumor). Interestingly, miR-26a, which was significantly associated with increased risk of both death and recurrence in platinum subgroup, was overexpressed in tumor as compared to the normal tissue (P<0.001), suggesting a potential oncogenic feature for this miRNA. We are currently validating these results. Our study provides strong evidence to support the application of circulating miRNAs as minimally invasive early diagnosis and prognosis/predictive biomarkers for EAC. Citation Format: Xia Pu, Jian Gu, Yuanqing Ye, Jaffer Ajani, Xifeng Wu. Circulating miRNAs as potential biomarkers for esophageal adenocarcinoma risk and clinical outcomes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2915. doi:10.1158/1538-7445.AM2014-2915