Prospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2020; 26(14): 1660-1673
Published online Apr 14, 2020. doi: 10.3748/wjg.v26.i14.1660
Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort
Robert Sean O’Neill, Sam Emmanuel, David Williams, Alina Stoita
Robert Sean O’Neill, David Williams, Alina Stoita, Department of Gastroenterology, St Vincent’s Hospital, Sydney 2010, Australia
Sam Emmanuel, Alina Stoita, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
Author contributions: O’Neill RS contributed to the writing of the manuscript; Emmanuel S provided the statistical analysis; Stoita A and Williams D as senior authors designed the prospective study, performed screening and revised the manuscript.
Institutional review board statement: The study protocol was reviewed and approved by the Ethics Committees of St Vincent’s Hospital, Sydney, NSW, Australia.
Clinical trial registration statement: This is not a clinical trial and therefore does not need to be registered under the clinical trials. Registration applies only to randomised control trials. There is no control arm, nor health intervention, the study looks at a new biomarker in an established pancreatic screening program. Results are not given to the patients and there is no intervention.
Informed consent statement: All study participants provided written informed consent prior to study enrolment.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Alina Stoita, FRACP, MBBS, Assistant Lecturer, Doctor, Department of Gastroenterology, St Vincent’s Hospital Sydney, 390 Victoria Street, Sydney 2010, Australia.
Received: December 24, 2019
Peer-review started: December 24, 2019
First decision: January 19, 2020
Revised: March 12, 2020
Accepted: March 27, 2020
Article in press: March 27, 2020
Published online: April 14, 2020

Pancreatic cancer (PC) is a leading cause of cancer related mortality worldwide, with poor survival due to late diagnosis. Currently, biomarkers have limited use in early diagnosis of PC. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) has been implicated as a potential serum biomarker in PC and other malignancies.


To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program.


A feasibility prospective single centre cohort study was performed. Participants recruited for yearly surveillance with endoscopic ultrasound (EUS) had serial fasting blood samples collected before EUS for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings: Normal; pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm; diffuse non-specific abnormalities; and neoplastic tumours. MIC-1/GDF15 serum levels were quantified using ELISA. Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging (MRI) or computed tomography.


One hundred twenty participants were prospectively recruited from 2011-2018. Forty-seven participants (39.2%) had an abnormal EUS and five participants (4.2%) were diagnosed with neoplastic tumours, three by EUS (two pancreatic and one liver) and two by MRI/computed tomography (breast cancer, bladder cancer), which were performed for follow up of abnormal EUS. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis [area under curve (AUC) = 0.814, P = 0.023]. Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm (AUC = 0.644) and neoplastic tumours noted on EUS (AUC = 0.793), however this was not significant (P = 0.188 and 0.081 respectively). Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS (P = 0.213). Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours (Median = 1039.6, interquartile range = 727.0-1977.7) compared to those diagnosed with a benign lesion (Median = 570.1, interquartile range = 460.7-865.2) on EUS and MRI (P = 0.012).


In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC. Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15. Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.

Keywords: Growth differentiation factor 15, Cytokines, Pancreatic neoplasms, Digestive system neoplasms, Pancreatic diseases, Biomarkers, Diagnostic screening programs

Core tip: In this prospective cohort study in an asymptomatic population at high risk of developing pancreatic cancer due to a genetic predisposition serum baseline macrophage inhibitory cytokine-1 or growth differentiation factor-15 was shown to be a significant predictor of neoplastic tumours (both pancreatic and extra-pancreatic).