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

Liver Cancer

Joong-Won Park¹  Hu Li²  Cheng Zhang²  Keun Soo Ahn³  Yong Hoon Kim³  Tae-Seok Kim³  Koo Jeong Kang³  Seoung Hoon Kim⁴  Sang-Jae Park⁴  Daniel R. O’Brien⁵  Lewis R. Roberts⁶  Hiroyuki Yamada⁷ 

[1] Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea;Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA;Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea;Department of Surgery, National Cancer Center, Goyang, Republic of Korea;Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA;Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA;Global Clinical Research Management, FUJIFILM Wako Pure Chemical Corporation, Tokyo, Japan;

关键词: α-fetoprotein;    des-γ-carboxyprothrombin;    hepatocellular carcinoma;    tp53;    ctnnb1;   

DOI  :  10.1159/000516957

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown