Plasma protein biomarkers for early detection of pancreatic ductal adenocarcinoma

Jingru Yu, Alexander Ploner, Maximilian Kordes, Matthias Löhr, Magnus Nilsson, Maria Evangelina Lopez de Maturana, Lidia Estudillo, Harald Renz, Alfredo Carrato, Xavier Molero, Francisco X Real, Núria Malats, Weimin Ye, Jingru Yu, Alexander Ploner, Maximilian Kordes, Matthias Löhr, Magnus Nilsson, Maria Evangelina Lopez de Maturana, Lidia Estudillo, Harald Renz, Alfredo Carrato, Xavier Molero, Francisco X Real, Núria Malats, Weimin Ye

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, mainly due to late diagnosis at advanced tumor stages. In this study, we aimed to identify plasma protein biomarkers for early detection of PDAC. Totally, 135 PDAC patients (early PDAC, Stage I/II, n = 71; advanced PDAC, Stage III/IV, n = 64), 13 benign lesions/chronic pancreatitis patients and 72 healthy individuals, with corresponding plasma samples from a case-control study in Sweden were included. A proximity extension assay was used to detect 92 cancer-related proteins, and an enzyme-linked immunosorbent assay/electrochemiluminescence immunoassay was used to detect CA19-9. Predictive features were selected from these 93 candidate proteins and three covariates in the Swedish participants, and then validated in Spanish participants, including 37 early PDAC patients, 38 advanced PDAC patients, 19 chronic pancreatitis patients and 36 healthy controls. A panel of eight proteins discriminating early PDAC from healthy individuals was identified, and the cross-validated area under the curves (AUCs) were 0.85 (95% confidence interval, 95% CI, 0.78-0.91) and 0.81 (95% CI, 0.70-0.92) in the Swedish and Spanish participants, respectively. Another eight-protein panel was predictive for classifying advanced PDAC from healthy controls in two populations, with cross-validated AUCs of 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.83-0.98), respectively. In conclusion, eight protein biomarkers were identified and externally validated, potentially allowing early detection of PDAC patients if validated in additional prospective studies.

Keywords: AUC; biomarkers; early diagnosis; pancreatic ductal adenocarcinoma; proteomics.

© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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