Clinical relevance of increased serum preneoplastic antigen in hepatitis C-related hepatocellular carcinoma

doi:10.3748/wjg.v26.i13.1463

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World Journal of Gastroenterology

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Clinical and Translational Research

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.

Corresponding author: Kiwamu Okita, MD, PhD, Honorary Director, Department of Internal Medicine, Shunan Memorial Hospital, Ikunoya Minami 1-10-1, Kudamatsu, Yamaguchi 7440033, Japan. okita@hcsdojinkai.or.jp

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
Processing time: 109 Days and 12.1 Hours

Abstract

BACKGROUND

The prognosis of hepatocellular carcinoma (HCC) patients remains poor despite advances in treatment modalities and diagnosis. It is important to identify useful markers for the early detection of HCC in patients. Preneoplastic antigen (PNA), originally reported in a rat carcinogenesis model, is increased in the tissues and serum of HCC patients.

AIM

To determine the diagnostic value of PNA for discriminating HCC and to characterize PNA-positive HCC.

METHODS

Patients with hepatitis C virus (HCV)-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.

RESULTS

Serum PNA concentrations were measured in 89 controls and 141 patients with HCV infections (50 hepatitis, 44 cirrhosis, and 47 HCC). Compared with control and non-HCC patients, PNA was increased in HCC. On receiver operating characteristic curve analysis, the sensitivity of PNA was similar to the HCC markers des-γ-carboxy-prothrombin (DCP) and α-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 were completely different for PNA, AFP, and DCP; glutamyl transpeptidase was highly correlated with PNA, but not with AFP or DCP, and was significantly higher in PNA-high patients than in PNA-low patients with HCV-related HCC.

CONCLUSION

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

Keywords: Serum preneoplastic antigen; Hepatitis C virus; Hepatocellular carcinoma; Des-γ-carboxy-prothrombin; α-Fetoprotein; Sensitivity; Specificity

Core tip: Despite advances in treatment modalities and diagnosis, the prognosis of hepatocellular carcinoma (HCC) patients remains poor. It is important to identify useful markers for the early detection of HCC. Preneoplastic antigen (PNA) is increased in the tissues and serum of HCC patients. Therefore, we investigated the diagnostic value of PNA to discriminate HCC. We found that PNA had a comparable diagnostic value to α-fetoprotein and des-γ-carboxy-prothrombin. PNA may have the potential to diagnose a novel type of HCC in which glutamyl transpeptidase is positively expressed, but α-fetoprotein or des-γ-carboxy-prothrombin is weakly or negatively expressed.