Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Diagnostic value of alpha-fetoprotein and prothrombin induced by vitamin K absence-II in serum, bile, and feces in hepatocellular carcinoma
Zi-Jun Chen, Xiang-Kun Wang, Chuang-Ye Han, Yong-Fei He, Tian-Yi Liang, Shu-Tian Mo, Guang-Zhi Zhu, Cheng-Kun Yang, Xin-Ping Ye, Zi-Li Lv, Shi-Fu Pang, Xiao-Dong Chen, Peng Wang, Tao Peng
Zi-Jun Chen, Chuang-Ye Han, Yong-Fei He, Tian-Yi Liang, Shu-Tian Mo, Guang-Zhi Zhu, Cheng-Kun Yang, Xin-Ping Ye, Zi-Li Lv, Tao Peng, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Xiang-Kun Wang, Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Shi-Fu Pang, Xiao-Dong Chen, AIage Life Science Corporation Ltd., Nanning, 530021, Guangxi Zhuang Autonomous Region, China
Peng Wang, Department of Health Management and Division of Physical Examination, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-corresponding authors: Peng Wang and Tao Peng.
Author contributions: Chen ZJ conceived and designed the study, provided the study materials and patients, and drafted the manuscript; Chen ZJ, Wang XK, and Han CY collated the data; He YF, Liang TY, Mo ST, Zhu GZ, Yang CK, Ye XP, Lv ZL, Pang SF, Chen XD, Wang P, and Peng T analyzed the data; All authors approved the manuscript.
Institutional review board statement: This study was conducted in accordance with ethical principles and was approved by the Ethical Review Committee of the First Affiliated Hospital of Guangxi Medical University, No. 2020 (KY-E-118).
Institutional animal care and use committee statement: No animal experiments were conducted in this study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The study data and materials are available upon request. Researchers or individuals interested in accessing the data or materials used in this research can contact
pengtaomu@163.com to request access. We are committed to ensuring transparency and facilitating the sharing of research resources while respecting any confidentiality or ethical considerations that may apply.
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 Peng, MD, PhD, Professor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
pengtaogmu@163.com
Received: January 18, 2025
Revised: March 6, 2025
Accepted: March 18, 2025
Published online: May 15, 2025
Processing time: 117 Days and 16.1 Hours
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer and was the third leading cause of cancer-related deaths worldwide in 2020.
AIM
To evaluate the diagnostic potential of key tumor markers in serum, bile, and fecal samples for detecting HCC.
METHODS
Blood, bile, and fecal samples were collected from patients (n = 265) with HCC and cholecystitis from Guangxi Medical University’s First Affiliated Hospital. Immunohistochemistry was performed on 69 HCC samples, and 16S ribosomal RNA sequencing was conducted on 166 fecal samples. Tumor marker cut-off values in bile and feces were determined using the Youden index, while serum biomarkers followed hospital standards. Diagnostic performance was evaluated using receiver operating characteristic analysis.
RESULTS
The areas under the curve (AUCs) for distinguishing HCC were 0.898, 0.904, and 0.859 for serum alpha-fetoprotein (AFP), prothrombin induced by vitamin K absence-II (PIVKA-II), and bile AFP, respectively. Serum AFP had the highest diagnostic value (80%) for early-stage HCC. Combination analysis found that bile AFP and serum PIVKA-II achieved the highest AUC of 0.965 (P < 0.001), suggesting that bile AFP may serve as a valuable complementary biomarker, particularly in cases where serum AFP is not significantly elevated. Additionally, bile AFP was positively correlated with Actinomyces, which plays a significant role in promoting tumorigenesis; and was negatively correlated with Faecalibacterium, which was associated with robust anticancer immune responses (P < 0.05). These findings suggest the potential role of gut microbiota in modulating AFP levels and HCC progression.
CONCLUSION
Bile AFP improved the sensitivity of HCC detection, with the combination of bile AFP and PIVKA-II demonstrating the highest AUC for HCC diagnosis. AFP is associated with poorer clinical outcomes.
Core Tip: This study evaluated the diagnostic potential of various biomarkers for hepatocellular carcinoma (HCC), with serum prothrombin induced by vitamin K absence-II (PIVKA-II) showing the highest diagnostic accuracy. However, serum alpha-fetoprotein (AFP) was more accurate for early HCC diagnosis. Bile AFP improved diagnostic performance and its combination with PIVKA-II achieved the highest area under the curve for HCC detection. Additionally, bile AFP was associated with poorer HCC clinical outcomes.
