Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers

Background Liver cancers are common malignancies that primarily include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Currently, the most commonly used serum markers for HCC are alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II), whil...

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Main Authors: Ling Luo, Xiaochen Wang, Xujian Peng, Runqiang Zhong, Xuejing Xuan, Haixiong Lin, Xianghua Lin, Chaohui Duan
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Language:English
Published: PeerJ Inc. 2025-07-01
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Online Access:https://peerj.com/articles/19712.pdf
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author Ling Luo
Xiaochen Wang
Xujian Peng
Runqiang Zhong
Xuejing Xuan
Haixiong Lin
Xianghua Lin
Chaohui Duan
author_facet Ling Luo
Xiaochen Wang
Xujian Peng
Runqiang Zhong
Xuejing Xuan
Haixiong Lin
Xianghua Lin
Chaohui Duan
author_sort Ling Luo
collection DOAJ
description Background Liver cancers are common malignancies that primarily include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Currently, the most commonly used serum markers for HCC are alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II), while the most commonly used serum markers for CCA are carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In recent years, many HCC diagnostic models using the combined detection of serum AFP, AFP-L3% and PIVKA-II have been established. For serum AFP, AFP-L3%, PIVKA-II and their many diagnostic models, there has been no clear guidance on the selection of these markers and their various combinations in the diagnosis of liver cancers. The aim of this study was to evaluate and compare the efficacy of these markers and the models that incorporate them in diagnosing HCC and CCA. This could assist in identifying the optimal patterns of serum AFP, AFP-L3% and PIVKA-II for the diagnosis of liver cancers. Methods Clinical data and the results of serum AFP, AFP-L3%, PIVKA-II, CEA and CA19-9 were collected from 117 patients with HCC, 28 patients with CCA and 101 patients with benign liver diseases. Laboratory tests and detection of serum tumor markers in liver cancer patients were conducted prior to treatments. Recently published diagnostic models for AFP, AFP-L3% and PIVKA-II detection were collected; these included GALAD, ASAP, GALAD-C, GAAP, C-GALAD, C-GALAD II and GAP-TALAD. Results Levels of AFP-L3%, PIVKA-II, GALAD, ASAP, GALAD-C, GAAP, C-GALAD and C-GALAD II significantly differed between the patient cohorts, with the highest levels seen in HCC, followed by CCA and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of CEA and CA19-9 significantly differed between cohorts, with the highest levels seen in CCA, followed by HCC and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of AFP and GAP-TALAD in HCC patients were significantly higher than those in patients with CCA and patients with benign liver diseases (p < 0.05), but there were no significant differences in levels of AFP and GAP-TALAD between patients with CCA and benign liver diseases (p > 0.05). In the diagnosis of HCC, GAP-TALAD, GALAD, C-GALAD, ASAP and GALAD-C showed the highest efficacy. In the diagnosis of overall liver cancers (HCC and CCA), GALAD-C, GAAP, GALAD, ASAP and C-GALAD showed the highest efficacy. In the diagnosis of early liver cancers (early HCC and CCA), GALAD, GALAD-C, GAAP, C-GALAD and ASAP showed the highest efficacy. Conclusions For serum AFP, AFP-L3% and PIVKA-II, diagnostic models of combined marker detection improved efficacy in the diagnosis of liver cancers. Diagnostic models GALAD, ASAP, GALAD-C and C-GALAD showed the highest efficacy in the diagnosis of HCC, overall liver cancers (HCC + CCA) and early liver cancers, and can be used preferentially in clinical practice.
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spelling doaj-art-bd1dba60ba734831aaee231424de4bdb2025-08-20T03:30:52ZengPeerJ Inc.PeerJ2167-83592025-07-0113e1971210.7717/peerj.19712Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancersLing LuoXiaochen WangXujian PengRunqiang ZhongXuejing XuanHaixiong LinXianghua LinChaohui DuanBackground Liver cancers are common malignancies that primarily include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Currently, the most commonly used serum markers for HCC are alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II), while the most commonly used serum markers for CCA are carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In recent years, many HCC diagnostic models using the combined detection of serum AFP, AFP-L3% and PIVKA-II have been established. For serum AFP, AFP-L3%, PIVKA-II and their many diagnostic models, there has been no clear guidance on the selection of these markers and their various combinations in the diagnosis of liver cancers. The aim of this study was to evaluate and compare the efficacy of these markers and the models that incorporate them in diagnosing HCC and CCA. This could assist in identifying the optimal patterns of serum AFP, AFP-L3% and PIVKA-II for the diagnosis of liver cancers. Methods Clinical data and the results of serum AFP, AFP-L3%, PIVKA-II, CEA and CA19-9 were collected from 117 patients with HCC, 28 patients with CCA and 101 patients with benign liver diseases. Laboratory tests and detection of serum tumor markers in liver cancer patients were conducted prior to treatments. Recently published diagnostic models for AFP, AFP-L3% and PIVKA-II detection were collected; these included GALAD, ASAP, GALAD-C, GAAP, C-GALAD, C-GALAD II and GAP-TALAD. Results Levels of AFP-L3%, PIVKA-II, GALAD, ASAP, GALAD-C, GAAP, C-GALAD and C-GALAD II significantly differed between the patient cohorts, with the highest levels seen in HCC, followed by CCA and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of CEA and CA19-9 significantly differed between cohorts, with the highest levels seen in CCA, followed by HCC and with the lowest levels seen in benign liver diseases (p < 0.05). Levels of AFP and GAP-TALAD in HCC patients were significantly higher than those in patients with CCA and patients with benign liver diseases (p < 0.05), but there were no significant differences in levels of AFP and GAP-TALAD between patients with CCA and benign liver diseases (p > 0.05). In the diagnosis of HCC, GAP-TALAD, GALAD, C-GALAD, ASAP and GALAD-C showed the highest efficacy. In the diagnosis of overall liver cancers (HCC and CCA), GALAD-C, GAAP, GALAD, ASAP and C-GALAD showed the highest efficacy. In the diagnosis of early liver cancers (early HCC and CCA), GALAD, GALAD-C, GAAP, C-GALAD and ASAP showed the highest efficacy. Conclusions For serum AFP, AFP-L3% and PIVKA-II, diagnostic models of combined marker detection improved efficacy in the diagnosis of liver cancers. Diagnostic models GALAD, ASAP, GALAD-C and C-GALAD showed the highest efficacy in the diagnosis of HCC, overall liver cancers (HCC + CCA) and early liver cancers, and can be used preferentially in clinical practice.https://peerj.com/articles/19712.pdfAlpha fetoproteinProtein induced by vitamin K absence or antagonist-IIHepatocellular carcinomaCholangiocarcinomaLiver cancersDiagnosis
spellingShingle Ling Luo
Xiaochen Wang
Xujian Peng
Runqiang Zhong
Xuejing Xuan
Haixiong Lin
Xianghua Lin
Chaohui Duan
Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
PeerJ
Alpha fetoprotein
Protein induced by vitamin K absence or antagonist-II
Hepatocellular carcinoma
Cholangiocarcinoma
Liver cancers
Diagnosis
title Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
title_full Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
title_fullStr Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
title_full_unstemmed Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
title_short Analysis of the optimal patterns of serum alpha fetoprotein (AFP), AFP-L3% and protein induced by vitamin K absence or antagonist-II (PIVKA-II) detection in the diagnosis of liver cancers
title_sort analysis of the optimal patterns of serum alpha fetoprotein afp afp l3 and protein induced by vitamin k absence or antagonist ii pivka ii detection in the diagnosis of liver cancers
topic Alpha fetoprotein
Protein induced by vitamin K absence or antagonist-II
Hepatocellular carcinoma
Cholangiocarcinoma
Liver cancers
Diagnosis
url https://peerj.com/articles/19712.pdf
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