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Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma

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Author(s)
Ahn K.S.O'Brien D.R.Kim Y.H.Kim T.-S.Yamada H.Park J.-W.Park S.-J.Kim S.H.Zhang C.Li H.Kang K.J.Roberts L.R.
Keimyung Author(s)
Ahn, Keun SooKim, Yong HoonKim, Tae SeokKang, Koo Jeong
Department
Dept. of Surgery (외과학)
Journal Title
Liver Cancer
Issued Date
2021
Volume
10
Issue
6
Keyword
α-FetoproteinDes-γ-carboxyprothrombinHepatocellular carcinomaTP53CTNNB1
Abstract
Introduction:
Serum α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy­pro­thrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data.

Methods:
From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the USA and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort.

Results:
Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (elevated levels of all 3 biomarkers [↑All]), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (53.8%) and RR patients (38.5%), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (30.8%) and ↑DCP (30.8%). The Wnt-β-catenin signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF-β and VEGF signaling were activated in ↑AFP&L3, whereas dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these findings by showing similar results between the test cohort and the remainder of the TCGA-LIHC cohort.

Conclusions:
Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile of HCC, especially for TP53 and CTNNB1. These findings may facilitate development of an evidence-based approach to treatment.
Keimyung Author(s)(Kor)
안근수
김용훈
김태석
강구정
Publisher
School of Medicine (의과대학)
Citation
Ahn K.S. et al. (2021). Associations of Serum Tumor Biomarkers with Integrated Genomic and Clinical Characteristics of Hepatocellular Carcinoma. Liver Cancer, 10(6), 593–605. doi: 10.1159/000516957
Type
Article
ISSN
1664-5553
Source
https://www.karger.com/Article/FullText/516957
DOI
10.1159/000516957
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44048
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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