Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 887-897
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.887
Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients
Hiroaki Takaya, Tadashi Namisaki, Mitsuteru Kitade, Naotaka Shimozato, Kosuke Kaji, Yuki Tsuji, Keisuke Nakanishi, Ryuichi Noguchi, Yukihisa Fujinaga, Yasuhiko Sawada, Soichiro Saikawa, Shinya Sato, Hideto Kawaratani, Kei Moriya, Takemi Akahane, Hitoshi Yoshiji
Hiroaki Takaya, Tadashi Namisaki, Mitsuteru Kitade, Naotaka Shimozato, Kosuke Kaji, Yuki Tsuji, Keisuke Nakanishi, Ryuichi Noguchi, Yukihisa Fujinaga, Yasuhiko Sawada, Soichiro Saikawa, Shinya Sato, Hideto Kawaratani, Kei Moriya, Takemi Akahane, Hitoshi Yoshiji, Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 6348522, Japan
Author contributions: Takaya H, Kitade M, Shimozato N, Kaji K, Tsuji Y, Nakanishi K, Noguchi R, Fujinaga Y, Sawada Y, Saikawa S, Sato S, Kawaratani H, Moriya K and Akahane T performed data analysis; Takaya H, Namisaki T and Yoshiji H contributed to the writing of the manuscript.
Institutional review board statement: Informed consent for the use of resected tissue was obtained from all patients, and the study protocol was approved by the Ethics Committee of Nara Medical University.
Informed consent statement: All study participants or their legal guardians provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: Informed consent for data sharing was not obtained but the presented data are anonymized, and risk of identification is low.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hiroaki Takaya, MD, PhD, Assistant Professor, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 6348522, Japan. htky@naramed-u.ac.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: March 21, 2019
Peer-review started: March 26, 2019
First decision: July 31, 2019
Revised: September 3, 2019
Accepted: September 10, 2019
Article in press: September 10, 2019
Published online: October 15, 2019
Abstract
BACKGROUND

Early diagnosis of hepatocellular carcinoma (HCC) is necessary to improve the prognosis of patients. However, the currently available tumor biomarkers are insufficient for the early detection of HCC. Acylcarnitine is essential in fatty acid metabolic pathways. A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis (SH) patients. In contrast, another study reported that the level of acetylcarnitine (AC2) - one of the acylcarnitine species - in non-SH patients with HCC was decreased vs that reported in those without HCC.

AIM

To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.

METHODS

Thirty-three non-SH patients (14 with HCC and 19 without HCC) were enrolled in this study. Blood samples were obtained from patients at the time of admission. The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry. The levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) were determined by enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.

RESULTS

The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC (P < 0.05). In contrast, the level of lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP) - AFP-L3% - was significantly higher in non-SH patients with HCC vs those without HCC (P < 0.05). However, the levels of total carnitine, free carnitine, AFP, des-γ-carboxy prothrombin, VEGF, and VEGFR-2 were not different between patients with and without HCC. The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC. The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2 (P < 0.05).

CONCLUSION

The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC. Further studies are warranted to investigate these differences.

Keywords: Acylcarnitine, Acetylcarnitine, Biomarker, Hepatocellular carcinoma, Angiogenesis, Carnitine palmitoyltransferase 1, Oxidative stress

Core tip: There is an urgent clinical need for the early diagnosis of hepatocellular carcinoma (HCC) in cirrhotic patients to improve prognosis. A recent study reported that a high level of acylcarnitine may be a useful biomarker for the early diagnosis of HCC in steatohepatitis (SH) patients. However, the level of acylcarnitine was significantly lower in non-SH patients with HCC than in those without HCC. Multivariate analysis showed that a low level of acylcarnitine was the only independent early diagnostic biomarker for non-SH HCC. Thus, the fatty acid metabolic pathways in SH HCC and non-SH HCC patients may be different.