Circulating histones as potential biomarkers of MASLD-MASH-HCC progression

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652079%3A_____%2F25%3A00644899" target="_blank" >RIV/86652079:_____/25:00644899 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.tandfonline.com/doi/abs/10.1080/17501911.2025.2611415" target="_blank" >https://www.tandfonline.com/doi/abs/10.1080/17501911.2025.2611415</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/17501911.2025.2611415" target="_blank" >10.1080/17501911.2025.2611415</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Circulating histones as potential biomarkers of MASLD-MASH-HCC progression

Popis výsledku v původním jazyce

Background Reliable biomarkers are warranted to identify patients with metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), at risk for developing hepatocellular carcinoma (HCC). Research and methods We evaluated whether circulating histones can predict this risk. Plasma histones were measured using imaging flow cytometry in patients with MASLD (n = 25), MASH (n = 25), HCC (n = 40), and 30 healthy controls. Results We detected (p < 0.05), compared to controls 1) elevated levels of H2A, H3, H2A/H2B/H3/H4, macroH2A1.1, macroH2A1.2 in MASLD/MASH and HCC, 2) decreased levels of macroH2A1.2/H2B/H3/H4 in MASLD/MASH and increased in HCC, 3) reduced H4 levels discriminating between MASH and non-MASH. Machine-learning analysis showed that being diabetic/dyslipidemic, having decreased H2A (p = 0.002) and H4 (p = 0.0156) levels favor MASH. Conclusions Our data indicate plasma histones H2A and H4 as new biomarkers of liver disease progression. The identification of histone-based biomarkers using imaging flow cytometry could provide a rapid approach to discriminate between non-MASH and MASH, and to predict the risk of HCC development. PLAIN LANGUAGE SUMMARY Patients with fatty liver disease linked to metabolism (MASLD or its more severe inflammatory form MASH) need better ways to spot who might later develop liver cancer (HCC). In this study, we measured different types of histones (proteins that bind our DNA and then float in the blood if cells die) using a special imaging technique in 25 people with MASLD, 25 with MASH, 40 with HCC, and 30 healthy people. We found clear differences several histones and histone complexes were higher in all patient groups than in healthy controls. Some histone levels were lower in MASLD/MASH but rose again in HCC, while histone H4 was particularly low in MASH and helped tell MASH apart from milder disease. Using machine learning, the strongest signals for having MASH (rather than a simpler fatty liver) were diabetes or high blood fats combined with lower circulating histones H2A and H4. Overall, blood levels of histones H2A and H4 look like promising new markers to track how serious the liver disease is, distinguish MASH from less severe forms, and possibly predict who will go on to develop liver cancer. This histone test is fast and could be useful in everyday practice.

Název v anglickém jazyce

Circulating histones as potential biomarkers of MASLD-MASH-HCC progression

Popis výsledku anglicky

Background Reliable biomarkers are warranted to identify patients with metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), at risk for developing hepatocellular carcinoma (HCC). Research and methods We evaluated whether circulating histones can predict this risk. Plasma histones were measured using imaging flow cytometry in patients with MASLD (n = 25), MASH (n = 25), HCC (n = 40), and 30 healthy controls. Results We detected (p < 0.05), compared to controls 1) elevated levels of H2A, H3, H2A/H2B/H3/H4, macroH2A1.1, macroH2A1.2 in MASLD/MASH and HCC, 2) decreased levels of macroH2A1.2/H2B/H3/H4 in MASLD/MASH and increased in HCC, 3) reduced H4 levels discriminating between MASH and non-MASH. Machine-learning analysis showed that being diabetic/dyslipidemic, having decreased H2A (p = 0.002) and H4 (p = 0.0156) levels favor MASH. Conclusions Our data indicate plasma histones H2A and H4 as new biomarkers of liver disease progression. The identification of histone-based biomarkers using imaging flow cytometry could provide a rapid approach to discriminate between non-MASH and MASH, and to predict the risk of HCC development. PLAIN LANGUAGE SUMMARY Patients with fatty liver disease linked to metabolism (MASLD or its more severe inflammatory form MASH) need better ways to spot who might later develop liver cancer (HCC). In this study, we measured different types of histones (proteins that bind our DNA and then float in the blood if cells die) using a special imaging technique in 25 people with MASLD, 25 with MASH, 40 with HCC, and 30 healthy people. We found clear differences several histones and histone complexes were higher in all patient groups than in healthy controls. Some histone levels were lower in MASLD/MASH but rose again in HCC, while histone H4 was particularly low in MASH and helped tell MASH apart from milder disease. Using machine learning, the strongest signals for having MASH (rather than a simpler fatty liver) were diabetes or high blood fats combined with lower circulating histones H2A and H4. Overall, blood levels of histones H2A and H4 look like promising new markers to track how serious the liver disease is, distinguish MASH from less severe forms, and possibly predict who will go on to develop liver cancer. This histone test is fast and could be useful in everyday practice.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Epigenomics

ISSN

1750-1911

e-ISSN

1750-192X

Svazek periodika

17

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1435-1446

Kód UT WoS článku

001654343500001

EID výsledku v databázi Scopus

2-s2.0-105026725451