Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study
AuthorDuell, Eric J.; Lujan-Barroso, Leila; Sala, Núria; Deitz McElyea, Samantha; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Weiderpass, Elisabete; Busund, Lill-Tove; Moi, Line; Muller, David; Aune, Dagfinn; Naccarati, Alessio; Panico, Salavatore; Tagliabue, Giovanna; Tumino, Rosario; Palli, Domenico; Kaaks, Rudolf; Katzke, Verena A.; Boeing, Heiner; Bueno-De-Mesquita, Hendrik Bastiaan; Peeters, Petra H.; Trichopoulou, Antonia; Lagiou, Pagona; Kotanidou, Anastasia; Travis, Ruth C.; Wareham, Nick; Khaw, Kay-Tee; Quirõs, Jose Ramõn; Rodríguez-Barranco, Miguel; Dorronsoro, Miren; Chirlaque, María Dolores; Ardanaz, Eva; Severi, Gianluca; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Brennan, Paul; Gunter, Marc; Scelo, Ghislaine; Cote, Greg; Sherman, Stuart; Korc, Murray
Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).
Accepted manuscript version. Published version available in International Journal of Cancer 2017, 141 (5):905–915 .