Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2023; 29(4): 706-730
Published online Jan 28, 2023. doi: 10.3748/wjg.v29.i4.706
Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers
Hai-Ning Liu, Can Yao, Xiao-Fan Wang, Ning-Ping Zhang, Yan-Jie Chen, Dong Pan, Guo-Ping Zhao, Xi-Zhong Shen, Hao Wu, Tao-Tao Liu
Hai-Ning Liu, Xiao-Fan Wang, Ning-Ping Zhang, Yan-Jie Chen, Xi-Zhong Shen, Hao Wu, Tao-Tao Liu, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Can Yao, Department of Gastroenterology and Hepatology, Minhang District Central Hospital, Fudan University, Shanghai 201199, China
Dong Pan, Department of Internet Technology Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Guo-Ping Zhao, Chinese National Human Genome Center at Shanghai, Zhujiang Hospital, Central Lab, Institute of Plant Physiology and Ecology, Shanghai Institute for Biological Sciences, Shanghai 200032, China
Author contributions: Liu HN, Yao C, and Wang XF contributed equally to this work; Liu HN, Wu H, and Liu TT conceived and designed the experiments; Liu HN, Yao C, and Wang XF drafted the manuscript; Liu HN, Yao C, Wang XF, and Pan D extracted the data; Liu HN, Zhang NP, and Chen YJ performed the statistical analyses; Zhao GP and Shen XZ revised the article; all authors finished reading and approving the final manuscript of this study.
Institutional review board statement: The study was reviewed and approved by the Zhongshan Hospital of Fudan University Institutional Review Board (Approval No. B2018-234).
Informed consent statement: The informed consent was waived from the patients.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at liu.taotao@zs-hospital.sh.cn. Participants gave informed consent for data sharing.
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: Tao-Tao Liu, MD, Doctor, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China. liu.taotao@zs-hospital.sh.cn
Received: September 18, 2022
Peer-review started: September 18, 2022
First decision: November 15, 2022
Revised: November 28, 2022
Accepted: December 21, 2022
Article in press: December 21, 2022
Published online: January 28, 2023
ARTICLE HIGHLIGHTS
Research background
Studies showed that blood carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) could be used to diagnose gastric cancer (GC) and colorectal cancer (CRC). Blood CA72-4 could be a potential biomarker to diagnose GC and CRC. A positive result in blood test would lead the subject to undergo further examinations.
Research motivation
Large-scale clinical application showed an extremely high false positive rate of CA72-4 for diagnosis, which leads to the waste of medical resources and heave social medical burden. The massive data and real-world diagnostic cohorts make it possible to further explore the diagnostic and economic value of biomarkers.
Research objectives
Through a real-world diagnostic cohort, we aimed to reassess the diagnostic and economic value of CEA, CA19-9, and CA72-4 for gastrointestinal malignant tumors in a large sample.
Research methods
Data from patients the medical examination center, outpatient department or inpatient department of Zhongshan Hospital of Fudan University from October 2006 to May 2018 were retrospectively evaluated. Four economic indicators were used to evaluate the economic value of tumor biomarkers. The diagnostic value of the three biomarkers was further evaluated.
Research results
The clinical benefits of CEA were higher than those of CA19-9, while the clinical benefits of CA72-4 were the lowest. The combination of biomarkers in the CRC and gastrointestinal malignant tumors significantly increased the AUC by less than 0.3, while that in GC did not. Compared to the economic indicators of the single biomarker CEA, the combination of biomarkers is not superior. At the threshold of 1.8 μg/L to 10.4 μg/L, all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.
Research conclusions
CEA had qualified diagnostic value for CRC and superior economic value for gastrointestinal cancers, especially for health checkup subjects above 65 years old while CA72-4 was not suitable as a diagnostic biomarker.
Research perspectives
In real world, many people undergo only blood tests but not gastrointestinal endoscopy when receiving a health checkup. Those undergone gastrointestinal endoscopy were at a higher risk of digestive diseases, which leads to an inevitable selection bias. Future researches may emphasize on the involvement of patients with normal CEA, CA19-9, CA72-4 Levels to decrease the number of false negative subjects.
