Case Control Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 659-669
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.659
N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer
Yan-Rong Wen, Xia-Wen Lin, Yu-Wen Zhou, Lei Xu, Jun-Li Zhang, Cui-Ying Chen, Jian He
Yan-Rong Wen, Xia-Wen Lin, Jian He, Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, Jiangsu Province, China
Yu-Wen Zhou, Lei Xu, Jun-Li Zhang, Cui-Ying Chen, Department of Research and Development, Sysdiagno (Nanjing) Biotech Co., Ltd, Nanjing 210008, Jiangsu Province, China
Co-first authors: Yan-Rong Wen and Xia-Wen Lin.
Co-corresponding authors: Cui-Ying Chen and Jian He.
Author contributions: All authors contributed to the study conception and design. Wen YR and Lin XW contributed equally to this work; Lin XW and He J collected the samples and conducted the data analysis; Zhou YW, Xu L, Zhang JL, and Chen CY performed N-glycans analysis; Wen YR and He J designed the research, analyzed data and wrote the manuscript. He J and Chen CY are the co-corresponding authors of this study. He J and Chen CY were involved in the experimental design and revision of the article. Specifically, He J assumed responsibility for the overall design of the subject, Chen CY focused on the experimental design of the N-glycan analysis.
Supported by fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University, No. 2021-LCYJ-MS-11.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and conformed to the ethical guidelines of the Declaration of Helsinki.
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at hjxueren@126.com.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian He, Doctor, PhD, Chief Doctor, Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. hjxueren@126.com
Received: October 5, 2023
Peer-review started: October 5, 2023
First decision: December 6, 2023
Revised: December 21, 2023
Accepted: January 18, 2024
Article in press: January 18, 2024
Published online: March 15, 2024
Abstract
BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates.

AIM

To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis.

METHODS

An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the “Glyco-model”.

RESULTS

The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%.

CONCLUSION

In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

Keywords: Glycomics, N-glycans, Biomarkers, Pancreatic cancer, Predictive modeling

Core Tip: This study employed a patient cohort to investigate the N-glycan signature of early-stage pancreatic cancer (PC). Serum N-glycans analysis was conducted to identify the serum biomarker signature associated with early-stage pancreatic ductal adenocarcinoma (PDAC), resulting in the identification of nine early-stage PDAC N-glycan signatures. Subsequently, utilizing these biosignatures, a diagnostic model named the “Glyco-model” was developed, demonstrating promising diagnostic performance across all stages of PC. The study revealed that the diagnostic sensitivity for stage I PDAC was determined to be 89.66%. Consequently, this diagnostic model exhibits potential as a prospective strategy for the early detection of PDAC.