Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Eric J. Duell, Leila Lujan-Barroso, Núria Sala, Samantha Deitz McElyea, Kim Overvad, Anne Tjonneland, Anja Olsen, Elisabete Weiderpass, Lill Tove Busund, Line Moi, David Muller, Paolo Vineis, Dagfinn Aune, Giuseppe Matullo, Alessio Naccarati, Salvatore Panico, Giovanna Tagliabue, Rosario Tumino, Domenico Palli, Rudolf Kaaks & 24 others Verena A. Katzke, Heiner Boeing, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Antonia Trichopoulou, Pagona Lagiou, Anastasia Kotanidou, Ruth C. Travis, Nick Wareham, Kay Tee Khaw, Jose Ramon Quiros, Miguel Rodríguez-Barranco, Miren Dorronsoro, María Dolores Chirlaque, Eva Ardanaz, Gianluca Severi, Marie Christine Boutron-Ruault, Vinciane Rebours, Paul Brennan, Marc Gunter, Ghislaine Scelo, Greg Cote, Stuart Sherman, Murray Korc

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)905-915
Number of pages11
JournalInternational Journal of Cancer
Volume141
Issue number5
DOIs
StatePublished - Sep 1 2017

Fingerprint

MicroRNAs
Pancreatic Neoplasms
Cohort Studies
Biomarkers
Prospective Studies
Adenocarcinoma
Logistic Models
Area Under Curve
ROC Curve
Case-Control Studies
Fasting
Polymerase Chain Reaction
Neoplasms

Keywords

  • biomarkers
  • cohort studies
  • microRNAs
  • pancreatic cancer

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Duell, E. J., Lujan-Barroso, L., Sala, N., Deitz McElyea, S., Overvad, K., Tjonneland, A., ... Korc, M. (2017). Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. International Journal of Cancer, 141(5), 905-915. https://doi.org/10.1002/ijc.30790

Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. / Duell, Eric J.; Lujan-Barroso, Leila; Sala, Núria; Deitz McElyea, Samantha; Overvad, Kim; Tjonneland, Anne; Olsen, Anja; Weiderpass, Elisabete; Busund, Lill Tove; Moi, Line; Muller, David; Vineis, Paolo; Aune, Dagfinn; Matullo, Giuseppe; Naccarati, Alessio; Panico, Salvatore; Tagliabue, Giovanna; Tumino, Rosario; Palli, Domenico; Kaaks, Rudolf; Katzke, Verena A.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Trichopoulou, Antonia; Lagiou, Pagona; Kotanidou, Anastasia; Travis, Ruth C.; Wareham, Nick; Khaw, Kay Tee; Ramon Quiros, Jose; 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.

In: International Journal of Cancer, Vol. 141, No. 5, 01.09.2017, p. 905-915.

Research output: Contribution to journalArticle

Duell, EJ, Lujan-Barroso, L, Sala, N, Deitz McElyea, S, Overvad, K, Tjonneland, A, Olsen, A, Weiderpass, E, Busund, LT, Moi, L, Muller, D, Vineis, P, Aune, D, Matullo, G, Naccarati, A, Panico, S, Tagliabue, G, Tumino, R, Palli, D, Kaaks, R, Katzke, VA, Boeing, H, Bueno-de-Mesquita, HB, Peeters, PH, Trichopoulou, A, Lagiou, P, Kotanidou, A, Travis, RC, Wareham, N, Khaw, KT, Ramon Quiros, J, Rodríguez-Barranco, M, Dorronsoro, M, Chirlaque, MD, Ardanaz, E, Severi, G, Boutron-Ruault, MC, Rebours, V, Brennan, P, Gunter, M, Scelo, G, Cote, G, Sherman, S & Korc, M 2017, 'Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study', International Journal of Cancer, vol. 141, no. 5, pp. 905-915. https://doi.org/10.1002/ijc.30790
Duell EJ, Lujan-Barroso L, Sala N, Deitz McElyea S, Overvad K, Tjonneland A et al. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. International Journal of Cancer. 2017 Sep 1;141(5):905-915. https://doi.org/10.1002/ijc.30790
Duell, Eric J. ; Lujan-Barroso, Leila ; Sala, Núria ; Deitz McElyea, Samantha ; Overvad, Kim ; Tjonneland, Anne ; Olsen, Anja ; Weiderpass, Elisabete ; Busund, Lill Tove ; Moi, Line ; Muller, David ; Vineis, Paolo ; Aune, Dagfinn ; Matullo, Giuseppe ; Naccarati, Alessio ; Panico, Salvatore ; Tagliabue, Giovanna ; Tumino, Rosario ; Palli, Domenico ; Kaaks, Rudolf ; Katzke, Verena A. ; Boeing, Heiner ; Bueno-de-Mesquita, H. Bas ; Peeters, Petra H. ; Trichopoulou, Antonia ; Lagiou, Pagona ; Kotanidou, Anastasia ; Travis, Ruth C. ; Wareham, Nick ; Khaw, Kay Tee ; Ramon Quiros, Jose ; 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. / Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. In: International Journal of Cancer. 2017 ; Vol. 141, No. 5. pp. 905-915.
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AU - Lujan-Barroso, Leila

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AU - Overvad, Kim

AU - Tjonneland, Anne

AU - Olsen, Anja

AU - Weiderpass, Elisabete

AU - Busund, Lill Tove

AU - Moi, Line

AU - Muller, David

AU - Vineis, Paolo

AU - Aune, Dagfinn

AU - Matullo, Giuseppe

AU - Naccarati, Alessio

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AU - Tumino, Rosario

AU - Palli, Domenico

AU - Kaaks, Rudolf

AU - Katzke, Verena A.

AU - Boeing, Heiner

AU - Bueno-de-Mesquita, H. Bas

AU - Peeters, Petra H.

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Kotanidou, Anastasia

AU - Travis, Ruth C.

AU - Wareham, Nick

AU - Khaw, Kay Tee

AU - Ramon Quiros, Jose

AU - Rodríguez-Barranco, Miguel

AU - Dorronsoro, Miren

AU - Chirlaque, María Dolores

AU - Ardanaz, Eva

AU - Severi, Gianluca

AU - Boutron-Ruault, Marie Christine

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AB - 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).

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