Plasma protein biomarkers for early detection of pancreatic ductal adenocarcinoma

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.

Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy

“…The main strength of our study is the inclusion of a relatively large number of patients with advanced PDAC, and the Olink PEA method used. Today, >800 articles have described this method, including more than 120 studies of patients with cancer, but only four studies of patients with PDAC [23,24,43,44]. With results from 737 samples from 363 patients, we confirmed IL-6 as a prognostic marker in PDAC; moreover, we described other proteins that had previously been reported in relation to PDAC to also have prognostic capabilities.…”

“…This sequence can then be quantified using quantitative real-time PCR (qPCR) [21,22]. We, and others, have demonstrated that this method can identify protein panels that could be useful for early diagnosis of PDAC [23,24]. In our previously published study, we found two protein indices for the identification of patients with PDAC from patients with non-malignant pancreatic diseases and healthy individuals.…”

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

“…However, CA19-9 also gives false positive results in benign pancreaticobiliary diseases [ 14 , 15 ]. Several studies reported a number of non-invasive diagnostic and/or prognostic markers of pancreatic cancer that have been tested alone or in combination, such as: CA125, CEA, CEACAM1, MUC1, MIC1/GDF15, REG3A/PAP1, PKM2 and AXL, as well as auto-antibodies, fecal microbiome signatures and myeloid-derived suppressor cells [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Yet, the clinical utility of these markers remains to be determined.…”

Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role

“…This panel can detect PC in plasma samples obtained from patients with unclassified stages (I–IV) of PC and shows prognostic potential . However, it remains unclear whether the ComB-CAN panel can detect early-stage (I/II) PC, given that early detection ability is the most important function of any cancer biomarker. − …”