Clinical and Translational Research
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2020; 26(13): 1463-1473
Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1463
Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma
Satoyoshi Yamashita, Akira Kato, Toshitaka Akatsuka, Takashi Sawada, Tomohide Asai, Noriyuki Koyama, Kiwamu Okita
Satoyoshi Yamashita, Akira Kato, Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Shimonoseki Medical Center, Shimonoseki, Yamaguchi 7500061, Japan
Toshitaka Akatsuka, Department of Physiology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama 3500495, Japan
Takashi Sawada, Tomohide Asai, Research and Development Division, Sekisui Medical Company Limited, Ryugasaki, Ibaraki 3010852, Japan
Noriyuki Koyama, Clinical Research Department, Eidia Company Limited, Chiyoda-ku, Tokyo 1010032, Japan
Noriyuki Koyama, Eisai Company Limited, Shinjuku-ku, Tokyo 1620812, Japan
Kiwamu Okita, Department of Internal Medicine, Shunan Memorial Hospital, Kudamatsu, Yamaguchi 7440033, Japan
Author contributions: Okita K, Sawada T, Asai T, and Koyama N developed the original idea for this study and designed the research protocol; Akatsuka T, Sawada T, and Asai T contributed to isolating specific antibodies and developing specific assays for this study; Yamashita S and Kato A contributed to patient enrollment and collecting clinical data; Sawada T, Asai T and Koyama N contributed to data analysis; All authors contributed to the interpretation of data and preparation of the manuscript.
Institutional review board statement: The study protocol was approved by the Human Ethics Committee of JCHO Shimonoseki Medical Center (Approval date: May 29, 2015).
Informed consent statement: The study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors Sawada T and Asai T are employees of Sekisui Medical Co., Ltd. Koyama N is an employee of Eisai Co., Ltd. Yamashita S, Kato A, Akatsuka T, and Okita K have no conflicts of interest to declare.
Data sharing statement: The datasets analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Kiwamu Okita, MD, PhD, Honorary Director, Department of Internal Medicine, Shunan Memorial Hospital, Ikunoya Minami 1-10-1, Kudamatsu, Yamaguchi 7440033, Japan.
Received: December 16, 2019
Peer-review started: December 16, 2019
First decision: February 18, 2020
Revised: March 6, 2020
Accepted: March 19, 2020
Article in press: March 19, 2020
Published online: April 7, 2020
Research background

The prognosis of hepatocellular carcinoma (HCC) patients remains poor despite advances in treatment modalities and diagnosis. The early detection of HCC allows patients to receive curative treatment and achieve long-term survival. It is important to identify useful markers for the early detection of HCC in patients.

Research motivation

Preneoplastic antigen (PNA), originally reported in a rat carcinogenesis model, is increased in the tissues and serum of HCC patients. However, the diagnostic value of PNA for discriminating HCC remains to be determined.

Research objectives

The objectives of this study are to determine the diagnostic value of PNA for discriminating HCC and to characterize PNA-positive HCC.

Research methods

Patients with hepatitis C virus-related hepatic disorders were prospectively enrolled in this study, which included patients with hepatitis, with cirrhosis, and with HCC. A novel enzyme-linked immunosorbent assay was developed to measure serum PNA concentrations in patients.

Research results

Compared with control and non-HCC patients, PNA was increased in HCC. The sensitivity of PNA was similar to the HCC markers des-γ-carboxy-prothrombin (DCP) and αα-fetoprotein (AFP), but the specificity of PNA was lower. There was no correlation between PNA and AFP and a significant but weak correlation between PNA and DCP in HCC patients. Importantly, the correlations with biochemical markers indicated that GTP was highly correlated with PNA, but not with AFP or DCP, and that it was significantly higher in PNA-high patients than in PNA-low patients with hepatitis C virus-related HCC.

Research conclusions

PNA may have the potential to diagnose a novel type of HCC in which GTP is positively expressed but AFP or DCP is weakly or negatively expressed.

Research perspectives

Further studies are needed to determine the diagnostic value of PNA for HCC patients in comparison with other HCC markers and to determine its potential for the detection of HCC nodules in the early stage. PNA-positive HCC may have an aggressive phenotype with a higher risk for disease progression and a poor prognosis. The prognostic value of PNA for survival will be determined in a follow-up evaluation of the patients enrolled in this study.