Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status.
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 Helicobacter 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. Quantitative real-time PCR (qRT-PCR) was used for cfmiRNA profiling. HP infection status was determined by immunoblotting assay. We identified a panel of 18 cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3.0E-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.
Shenzhen Key Laboratory of Translational Medicine of Tumor, Shenzhen University School of Medicine, Shenzhen 518060, China, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA, Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA and Department of Surgery and Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA rzhai@szu.edu.cn.
Rihong
R
Zhai
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Yongyue
Y
Wei
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Li
L
Su
Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada.
Geoffrey
G
Liu
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA and.
Mathew H
MH
Kulke
Department of Surgery and.
John C
JC
Wain
Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
David C
DC
Christiani
D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D035683:MicroRNAs