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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study
Tao Yue, Hui Lu, Xiao-Mei Yao, Xia Du, Ling-Ling Wang, Dan-Dan Guo, Yi-Ming Liu
Tao Yue, Dan-Dan Guo, Yi-Ming Liu, Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Tao Yue, Department of Gerontology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Hui Lu, Department of Ophthalmology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Xiao-Mei Yao, Department of Gerontology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong Province, China
Xia Du, Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China
Ling-Ling Wang, Department of Neurology, Yantaishan Hospital, Yantai 264001, Shandong Province, China
Author contributions: Yue T and Liu YM interpreted the patient data, and were major contributors in writing the manuscript; Lu H and Yao XM analyzed and interpreted the data; Du X, Guo DD and Wang LL performed the ELISA examination of serum; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81771373; and Key Research and Development Plan of Zibo City, No. 2019ZC010169 and No. 2019ZC010166.
Institutional review board statement: The study was approved by the Ethics Committee of Qilu Hospital of Shandong University.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at liuym@sdu.edu.cn.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yi-Ming Liu, MD, PhD, Chief Doctor, Professor, Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No.107, Wenhua West Road, Jinan 250012, Shandong Province, China. liuym@sdu.edu.cn
Received: January 30, 2020
Peer-review started: January 30, 2020
First decision: April 21, 2020
Revised: May 9, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: June 26, 2020
ARTICLE HIGHLIGHTS
Research background
Multiple system atrophy (MSA) is a serious progressive neurodegenerative disease. The early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. There is an urgent need for biomarkers for early diagnosis, prognostic prediction of disease progression, and monitoring the therapeutic response.
Research motivation
Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β superfamily. Abnormal concentrations of GDF15 are considered to have a close association with neurodegenerative diseases and might be a potential biomarker for early diagnosis. It has not been previously reported whether serum GDF15 levels are also higher in patients with MSA.
Research objectives
This study aimed to determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients.
Research methods
A case-control study was conducted, which included 49 MSA patients, 50 Parkinson’s disease (PD) patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay and the differences between the MSA, PD and control groups were analyzed.
Research results
Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels might be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively).
Research conclusions
We found that serum GDF15 levels in MSA patients were significantly higher compared with PD patients and healthy controls. Male patients with MSA had higher serum GDF15 levels than female patients, and serum GDF15 levels were also higher in those with disease duration of more than 3 years. The receiver-operating characteristic curve analysis revealed that serum GDF15 levels had high specificity, while the sensitivity seemed unsatisfactory in the differential diagnosis between MSA and PD. Serum GDF15 levels might be a potential diagnostic biomarker for MSA patients.
Research perspectives
This study revealed that serum GDF15 might be a potential diagnostic biomarker in MSA. To further explore whether serum GDF15 levels are consistent with clinical manifestations requires studies with larger sample sizes in the future. The difference between serum GDF15 and cerebrospinal fluid GDF15 should be considered.
