Observational Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2018; 24(25): 2733-2740
Published online Jul 7, 2018. doi: 10.3748/wjg.v24.i25.2733
Transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma
Yang An, Song Gao, Wen-Chao Zhao, Bao-An Qiu, Nian-Xin Xia, Peng-Jun Zhang, Zhen-Ping Fan
Yang An, Wen-Chao Zhao, Bao-An Qiu, Nian-Xin Xia, Department of Hepato-Biliary-Pancreatic Surgery, Navy General Hospital of Chinese People’s Liberation Army, Beijing 100048, China
Song Gao, Peng-Jun Zhang, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing 100142, China
Zhen-Ping Fan, Liver Disease Center for Cadre Medical Care, Beijing 302 Military Hospital, Beijing 100039, China
Author contributions: An Y, Gao S, Fan ZP, and Zhang PJ designed the study; An Y, Gao S, Zhao WC, and Xia NX performed the research; An Y, Gao S, Qiu BA, Fan ZP, and Zhang PJ analyzed the data; An Y and Gao S wrote the paper; Fan ZP and Zhang PJ revised the manuscript for final submission; An Y and Gao S contributed equally to this study; Fan ZP and Zhang PJ are the co-corresponding authors.
Supported by the National Key R and D Program of China, No. 2016YFC0106604; and the National Natural Science Foundation of China, No. 81502591.
Institutional review board statement: The study was reviewed and approved by the Peking University Cancer Hospital & Institute review board.
Informed consent statement: All study participants or their legal guardian provided written informed consent prior to study enrollment.
Conflict-of-interest statement: We declare that we have no financial or personal relationships with other individuals or organizations that can inappropriately influence our work and that there is no professional or other personal interest of any nature in any product, service, and/or company that could be construed as influencing the position presented in or the review of the manuscript.
Data sharing statement: No additional data are available.
STROBE statement: The guidelines of the STROBE Statement have been adopted in our manuscript.
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/
Correspondence to: Zhen-Ping Fan, MD, Doctor, The Liver Disease Center for Cadre Medical Care, Beijing 302 Military Hospital, Xi Si Huan Zhong Road 100, Beijing 100039, China. fanzp302@126.com
Telephone: +86-1-66933466 Fax: +86-1-63879735
Received: March 22, 2018
Peer-review started: March 22, 2018
First decision: April 10, 2018
Revised: April 14, 2018
Accepted: June 2, 2018
Article in press: June 2, 2018
Published online: July 7, 2018
Processing time: 104 Days and 23.9 Hours
Abstract
AIM

To understand the cellular and molecular changes in peripheral blood that can lead to the development of hepatocellular carcinoma (HCC) and provide new methods for its diagnosis and treatment.

METHODS

Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-β (TGF-β)+ regulatory cells (Tregs) in the peripheral blood was measured, and the expression of TGF-β was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-β (rhTGF-β) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were evaluated.

RESULTS

The expression of TGF-β and the percentage of TGF-β+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-β expression group, the high TGF-β expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-β+ Treg groups, suggesting that TGF-β and TGF-β+ Tregs were negatively correlated with the overall survival of the patients. In addition, rhTGF-β promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor proliferation.

CONCLUSION

The results showed that TGF-β may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-β and TGF-β+ Tregs may serve as new markers for predicting a poor prognosis in HCC.

Keywords: Hepatocellular carcinoma; Transforming growth factor-β; Regulatory cells; Peripheral blood mononuclear cells; Interleukin-6

Core tip: We aimed to understand the cellular and molecular changes in peripheral blood of hepatocellular carcinoma (HCC) and provide new methods for its diagnosis and treatment. The results showed that transforming growth factor-β (TGF-β) may promote tumor growth and proliferation by inducing the production of interleukin-6, and TGF-β and TGF-β+ regulatory cells may serve as new markers for predicting poor prognosis of HCC.