Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2018; 24(32): 3650-3662
Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3650
Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes
Wen-Jie Zheng, Min Yao, Miao Fang, Li Wang, Zhi-Zhen Dong, Deng-Fu Yao
Wen-Jie Zheng, Miao Fang, Deng-Fu Yao, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Min Yao, Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Li Wang, Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Zhi-Zhen Dong, Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Zheng WJ and Yao M contributed equally to this work and wrote the first draft; Fang M performed the cell experiments; Wang L analyzed data; Zheng WJ conducted the animal model study; Dong ZZ and Yao DF revised the manuscript. All authors approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81673241 and No. 81702419; Projects of Jiangsu Medical Science, No. BE2016698; Jiangsu Graduate Innovation, No. KYCX17_1934; Nantong Health and Family Planning Commission, No. WQ2016083; and National Int S&T Cooperation Program, No. 2013DFA32150.
Institutional animal care and use committee statement: The study protocol was approved by the Animal Medical Ethics Committee of Affiliated Hospital of Nantong University.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional unpublished data are available.
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:
Correspondence to: Deng-Fu Yao, MD, PhD, Professor, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, Jiangsu Province, China.
Telephone: +86-513-85052523
Received: May 18, 2018
Peer-review started: May 19, 2018
First decision: June 6, 2018
Revised: June 14, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 28, 2018
Processing time: 101 Days and 4.4 Hours
Research background

Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide with a multi-factorial, multistep, complex process, and poor prognosis. Early diagnosis of HCC at an early stage is of the utmost importance. This found a new molecular biomarker to monitor the malignant transformation of hepatocytes.

Research motivation

Although serum alpha fetoprotein (AFP) level is a useful tumor marker for the detection and monitoring of HCC, the false-negative rate with AFP level alone may be as high as 40% for patients with early stage HCC. Even in patients with advanced HCC, the AFP levels may remain normal in 15%-30% of the patients. New specific markers, such as circulating HS-GGT, HS-AFP or AFP-L3, miRNA, GPC-3, and GP73, have been developed to improve the sensitivity, specificity, early detection, and prediction of prognosis. However, the overall results have been unsatisfactory.

Research objectives

The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence, and to give adequate treatment for HCC. It has many characteristics, such as fast infiltrating growth, metastasis in early stage, high-grade malignancy, and poorly therapeutic efficacy, thus the prognosis is poor and early detection is of the utmost importance. The present study focused on exploring the relationship between dynamic expression of HMGB-3 and malignant transformation of hepatocytes.

Research methods

Dynamic models of rat hepatocarcinogenesis were made to investigate the expression of the high mobility group box (HMGB) family. HMGB3 expression was measured at the protein level by immunohistochemistry or Western blotting and at the mRNA level by real time PCR. Human HMGB3 expression was evaluated using bioinformatics databases and its mechanisms were analyzed in vitro. Xenograft growth was also measured.

Research results

HMGB3 expression was upregulated through the malignant transformation of liver cells in vivo.

Research conclusions

The upregulation of liver HMGB3 expression was found by dynamic model of hepatocytes malignant transformation with the alterations of rat liver histopathology. This was confirmed by mining HMGB3 expression in human HCC tissues in bioinformatic databases. Further studies elucidating the role HMGB3 plays in regulating HCC progression, suggests that HMGB3 could be a novel marker for early diagnosis or a molecular therapy target.

Research perspectives

HMGB3 has been confirmed as one of the key molecules in the HMGB family with HCC development. However, the molecular mechanisms of the upregulation of HMGB3 expression and its important role in hepatocarcinogenesis should be clarified in promoting proliferation of HCC cells and tumor growth and regulating cell cycle and DNA replication pathways in the future.