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
Research background

Early detection of pancreatic cancer (PC) is a key priority in order to improve survival. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) is a novel candidate tumour marker for PC with initial results proving to be elevated in the serum of patients with PC compared to healthy controls and those with benign lesions.

Research motivation

We need an early sensitive and specific serological marker that can be used as a first line screening tool in patients at risk of PC and help select cases that need further investigations, such as endoscopic ultrasound (EUS) or magnetic resonance imaging. This study evaluates the role of MIC-1/GDF15 in patients at high risk of developing PC.

Research objectives

This is a pilot study 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 and correlate with imaging finding.

Research methods

Participants recruited for yearly surveillance with EUS had serial fasting blood samples collected for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings. MIC-1/GDF15 serum levels were quantified using ELISA and correlations of MIC-1/GDF15 with population variables and imaging findings were performed. A receiver operating characteristic curve of MIC-1/GDF15 was generated for its ability to determine the presence or absence of neoplastic tumours , pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm and diffuse non-specific abnormality using serum levels adjusted for variables shown to either be significantly related to MIC-1/GDF15 concentrations in this study, or have shown to correlate with MIC-1/GDF15 in previous studies.

Research results

One hundred twenty participants were recruited over 8 years. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operating characteristic curve analysis. 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. Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours compared to those diagnosed with a benign lesion.

Research conclusions

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 raised serum MIC-1/GDF15 and abnormal EUS.

Research perspectives

This pilot study is the first of its kind to implement MIC-1/GDF15 as a screening tool in an asymptomatic population with a genetic predisposition of developing PC. Our study is a feasibility study and we hope our results will start a new wave of research (larger, multicentric, prospective trials) into investigating the role of this biomarker in early detection of neoplastic tumours to validate our finding and provide further characterisation of this biomarker.