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Serum biomarker signature-based liquid biopsy for diagnosis of early-stage pancreatic cancer

Authors: Linda D. Mellby, Andreas P. Nyberg, Julia S. Johansen, Christer Wingren, BÝrge G. Nordestgaard, Stig E. Bojesen, Breeana L. Mitchell, Brett C. Sheppard, Rosalie C. Sears, Carl A.K. Borrebaeck

Summary:

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of < 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort.

Patients and Methods: The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC.

Results: Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96.

Conclusion: This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.

Source: Journal of Clinical Oncology, 2018; JCO.2017.77.665