Retrospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2024; 16(6): 2463-2475
Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2463
Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers
Li He, Cui Zhang, Lan-Lan Liu, Li-Ping Huang, Wen-Jing Lu, Yuan-Yuan Zhang, De-Yong Zou, Yu-Fei Wang, Qing Zhang, Xiao-Li Yang
Li He, Qing Zhang, School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong Province, China
Li He, Qing Zhang, Department of Organ Transplantation, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
Cui Zhang, Lan-Lan Liu, Wen-Jing Lu, Yuan-Yuan Zhang, De-Yong Zou, Yu-Fei Wang, Xiao-Li Yang, Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, Beijing 100039, China
Li-Ping Huang, Department of Laboratory Medicine, Jingyu County People’s Hospital, Baishan 135200, Jilin Province, China
Xiao-Li Yang, School of Laboratory Medicine, Weifang Medical University, Weifang 261053, Shandong Province, China
Co-first authors: Li He and Cui Zhang.
Co-corresponding authors: Qing Zhang and Xiao-Li Yang.
Author contributions: He L and Zhang C designed and performed the research; He L and Zhang C drafted the manuscript; Liu LL and Huang LP designed the research and supervised the report; Lu WJ, Zhang YY, Zou DY and Wang YF contributed to the analysis; Zhang Q and Yang XL provided clinical advice; Zhang Q and Yang XL supervised the report. All authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. He L and Zhang C contributed equally to this work as co-first authors. The reasons for designating He L and Zhang C as co-first authors are threefold. Firstly, their individual contributions to the project were equally significant and complementary. He L provided the design of the study, and Zhang C provided great help and reference in her writing. Secondly, the decision to designate them as co-first authors reflects the collaborative spirit and teamwork that characterized their contributions. Their ability to work together effectively, sharing ideas and responsibilities, was a key factor in the project's progress and ultimate success. Lastly, contributed efforts of equal substance throughout the research process. The choice of these researchers as co-first authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. The reasons for designating Zhang Q and Yang XL as co-corresponding author are twofold. Firstly, Zhang Q and Yang XL, each possess unique and complementary expertise that is crucial to the success of the research project. Zhang Q with his profound knowledge in the field of biochemistry, brings a wealth of experience in experimental design and data analysis. Yang XL, on the other hand, excels in the area of computational biology, providing invaluable insights through modeling and simulations. Secondly, their collaborative spirit and commitment to teamwork have been instrumental in ensuring the smooth progress of the project. They have demonstrated excellent communication skills and a shared vision for the research, ensuring that all aspects of the study are addressed comprehensively. By designating them as co-corresponding authors, we aim to recognize their equal contribution and leadership in this important work.
Supported by National Natural Science Foundation of China, No. 81972696.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Third Medical Centre of Chinese PLA General Hospital (No. KY2021-009).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Li Yang, DPhil, Chief Technician, Department of Laboratory Medicine, The Third Medical Centre of Chinese PLA General Hospital, No. 69 Yongding Road, Haidian District, Beijing 100039, China. yangxiaolitwins@163.com
Received: January 23, 2024
Peer-review started: January 23, 2024
First decision: January 30, 2024
Revised: February 12, 2024
Accepted: April 1, 2024
Article in press: April 1, 2024
Published online: June 15, 2024
Processing time: 144 Days and 0.8 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC.

AIM

To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers.

METHODS

A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA).

RESULTS

The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram.

CONCLUSION

Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

Keywords: Hepatocellular carcinoma; Alpha-fetoprotein-negative; Diagnostic; Nomogram; Biomarker

Core Tip: The primary objective of this study was to develop a diagnostic model that can effectively identify patients with alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) using biomarkers. While previous research has demonstrated the usefulness of combining serological markers for diagnosing HCC, there have been limited investigations on diagnostic models specifically for AFP-negative HCC. Clinicians currently face the challenge of identifying individuals at high risk for early HCC, especially when patients exhibit normal levels of AFP. Early detection plays a crucial role in enabling timely surgical interventions, improving treatment outcomes, and ultimately enhancing the chances of survival for patients with HCC.