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Characteristics of TP53 and CTNNB1 mutation according to the serum tumor markers in hepatocellular carcinoma

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AHBPS

Annals of Hepato-Biliary-Pancreatic Surgery

www.ahbps.org S38

Characteristics of TP53 and CTNNB1 mutation according to the serum tumor markers in hepatocellular carcinoma

Keun Soo AHN*

,1

, Koo Jeong KANG

1

, Tae-Seok KIM

1

, Yong Hoon KIM

1

, Joong-Won PARK

2

, Sang-Jae PARK

3

, Seoung Hoon KIM

3

1

Department of Surgery, Keimyung University Dongsan Hospital, Daegu, Korea

2

Department of Internal Medicine, National Cancer Center, Goyang, Korea

3

Department of Surgery, National Cancer Center, Goyang, Korea

LV-BEST-OP-3

Introduction: Serum alpha-fetoprotein (AFP), Lens culinaris agglutinin−reactive AFP (AFP-L3), and des-gamma-carboxyprothrom- bin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and se- rum biomarkers are unclear.

Methods: We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TC- GA-LIHC) to examine their associations with serum biomarker levels and clinical data. From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the United States 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 (↑All), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP pa- tients (n = 7 [53.8%]) and RR patients (n = 10 [38.5%]), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients.

TP53 sequence variants were associated with ↑AFP (n = 8 [30.8%]) and ↑DCP (n = 4 [30.8%]). The Wnt signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF and VEGF signaling are activated in high AFP&L3, while dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these finding using the remainder of the TCGA-LIHC cohort and showed similar results to the test cohort.

Conclusions: Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile.

pISSN: 2508-5778ㆍeISSN: 2508-5859

Ann Hepatobiliary Pancreat Surg 2021;25 Suppl 1:S38 https://doi.org/10.14701/ahbps.LV-BEST-OP-3

Corresponding Author: Keun Soo AHN (ahnksmd@gmail.com) Presenter: Keun Soo AHN (ahnksmd@gmail.com)

Copyright Ⓒ The Korean Association of Hepato-Biliary-Pancreatic Surgery

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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