Evidence map›Paper›PMID 41074468›Full record

ArticleJournal of clinical laboratory analysis2025

Characterization of PIVKA-II Molecular Forms via Size Exclusion Chromatography and Hydrophobic Interaction Chromatography in HCC Patients.

Yoshiyuki Kitamura, Katsumi Aoyagi

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Article in Journal of clinical laboratory analysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Yoshiyuki KitamuraResearch and Development Division, Fujirebio Inc., Tokyo, Japan.ORCID https://orcid.org/0009-0007-2961-1701
Katsumi AoyagiResearch and Development Division, Fujirebio Inc., Tokyo, Japan.ORCID https://orcid.org/0000-0003-3818-7985

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProtein induced by the absence of vitamin K or antagonist-II (PIVKA-II) is an important serological biomarker for the diagnosis of hepatocellular carcinoma (HCC). The crucial epitope of PIVKA-II comprises a series of Glu residues located in the Glu-Gla domain. The other antibody required for the PIVKA-II sandwich immunoassay recognizes prothrombin fragments 1 and 2. However, the molecular diversity of these regions has not been well documented.

methodsPIVKA-II immuno-reactivities in blood taken from HCC patients were analyzed by size exclusion chromatography (SEC) and hydrophobic interaction chromatography (HIC). Obtained fractions were subsequently tested using MU-3 monoclonal antibody (mAb) and a polyclonal anti-prothrombin antibody (pAb). Immuno-reactivity in each fraction was analyzed by an inhibition assay using prothrombin fragments and by a sandwich immunoassay.

resultsSEC analysis of three paired serum and plasma samples gave a single peak of PIVKA-II immuno-reactivity corresponding to the expected molecular mass. However, HIC analysis using three paired sets and 14 HCC specimens revealed immuno-reactivity present in two distinct peaks of either low (peak-L: an elution position of 300-500 mM ammonium sulfate) or high (peak-H: an elution position of 100-300 mM ammonium sulfate) hydrophobicity or both peaks together. Immuno-reactivity of peak-L was inhibited by human prothrombin fragment-1 and detected by mAbs that recognize prothrombin-1. Immuno-reactivity of peak-H was inhibited by human prothrombin fragment-2 and detected by mAbs for prothrombin-2.

conclusionsThese results demonstrate PIVKA-II exhibits molecular diversity, suggesting its potential as a diagnostic tool. This finding will contribute to further understanding of HCC and improve diagnostic accuracy.

Indexed as

BiomarkersCarcinoma, HepatocellularChromatography, GelLiver NeoplasmsProtein PrecursorsProthrombinFemaleHumansHydrophobic and Hydrophilic InteractionsMaleMiddle AgedacarboxyprothrombinBiomarkersProtein PrecursorsProthrombinbloodhepatocellular carcinomahydrophobic interaction chromatographyimmuno‐reactivityPIVKA‐II

Identifiers

PMID41074468
PMCPMC12618172

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