Circulating small extracellular vesicle-derived splicing factor 3b subunit 4 as a non-invasive diagnostic biomarker of early hepatocellular carcinoma

Circulating small extracellular vesicle-derived splicing factor 3b subunit 4 as a non-invasive diagnostic biomarker of early hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3...

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Bibliographic Details
Published in:Journal of experimental & clinical cancer research Vol. 42; no. 1; pp. 1 - 288
Main Authors: Son, Ju A, Weon, Ji Hyang, Baek, Geum Ok, Ahn, Hye Ri, Choi, Ji Yi, Yoon, Moon Gyeong, Cho, Hyo Jung, Cheong, Jae Youn, Eun, Jung Woo, Kim, Soon Sun
Format: Journal Article
Language:English
Published: London BioMed Central Ltd 30-10-2023
BioMed Central
BMC
Subjects:
Autoantibodies
Autoimmunity
Biobanks
Biomarker
Biomarkers
Biopsy
Cancer
Carcinoma
Cell culture
Cell cycle
Enzyme-linked immunosorbent assay
Enzymes
Ethylenediaminetetraacetic acid
Extracellular vesicles
Gene expression
Glycoproteins
Hepatitis
Hepatitis C
Hospitals
Liquid biopsy
Liver cancer
Liver cirrhosis
Liver diseases
Liver Neoplasms
Medical prognosis
Myeloid-derived suppressor cell
Patients
Proteins
RNA
RNA sequencing
SF3B4
Somatotropin
Surveillance
Ultrasonic imaging
South Korea
Germany
Taiwan
United States > US
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Summary:Background Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3B4 expression and immune cell infiltration. Methods An enzyme-linked immunosorbent assay (ELISA) was used to detect SF3B4 levels in plasma samples obtained from healthy controls (HCs) and patients with chronic hepatitis, liver cirrhosis, and HCC. The expression levels of autoantibodies that detect SF3B4 in the plasma samples of each group of patients were measured. Small extracellular vesicles (EVs) were isolated from patient sera, and the expression levels of EV-SF3B4 were measured using quantitative reverse transcription PCR. Results ELISA results confirmed that the expression levels of SF3B4 proteins and autoantibodies in the plasma of patients with HCC were higher than those in HCs. However, their diagnostic performance was not better than that of alpha-fetoprotein (AFP). The mRNA expression of SF3B4 in serum EV increased but not in the buffy coat or serum of patients with HCC. Serum EV-SF3B4 displayed better diagnostic power than AFP for all stages of HCC (AUC = 0.968 vs. 0.816), including early-stage HCC (AUC = 0.960 vs. 0.842), and this was consistent in the external cohort. Single-cell RNA sequencing indicated that SF3B4 expression was correlated with myeloid-derived suppressor cells. The Tumor Immune Estimation Resource database reconfirmed the correlation between SF3B4 expression and immune cell infiltration in HCC. Conclusions SF3B4 may be associated with tumor immune infiltration in HCC, and EV-SF3B4 shows potential as a novel non-invasive diagnostic biomarker of HCC. Keywords: Biomarker, Myeloid-derived suppressor cell, Liquid biopsy, Liver Neoplasms, SF3B4
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ISSN:1756-9966
0392-9078
1756-9966
DOI:10.1186/s13046-023-02867-y