Meta-Analysis
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World J Gastroenterol. Jun 28, 2014; 20(24): 7971-7978
Published online Jun 28, 2014. doi: 10.3748/wjg.v20.i24.7971
Roles of Tregs in development of hepatocellular carcinoma: A meta-analysis
Hong-Qiang Zhao, Wei-Min Li, Zhong-Qiou Lu, Yong-Ming Yao
Hong-Qiang Zhao, Medical School of Chinese People’s Liberation Army, Beijing 100853, China
Wei-Min Li, Department of Hepatobiliary Surgery, the 309th Hospital of Chinese People’s Liberation Army, Beijing 100091, China
Zhong-Qiou Lu, Department of Emergency Care, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China
Yong-Ming Yao, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China
Author contributions: Zhao HQ and Li WM contributed equally to this work, who designed the study, analyzed the data and wrote the manuscript; Lu ZQ contributed to the discussion and wrote the manuscript; Yao YM as the corresponding author reviewed the manuscript and made significant revisions.
Supported by National Natural Science Foundation of China, No. 81130035, No. 81372054, No. 81071545, and No. 81121004; and the National Basic Research Program of China, No. 2012CB518102
Correspondence to: Yong-Ming Yao, MD, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing 100048, China. c_ff@sina.com
Telephone: +86-10-66867394 Fax: +86-10-68989955
Received: October 8, 2013
Revised: February 19, 2014
Accepted: March 4, 2014
Published online: June 28, 2014
Abstract

AIM: To assess systematically the association between regulatory T cells (Tregs) and hepatocellular carcinoma (HCC).

METHODS: We searched Medline, Embase and Wanfang databases for literature on the populations of Tregs in HCC patients and controls, using the pooled OR and 95%CIs for assessment. There were no limitations with respect to publication date or language. The references of qualifying articles were also searched. We excluded studies with unclear data or overlapping studies. Twenty-three studies met our criteria, and the quality of these studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN). The meta-analysis of association between Tregs and HCC was undertaken using the random-effects approach, as described by DerSimonian and Laird. Subgroup analysis was performed when at least three studies were available. Potential publication bias was assessed by visual inspection of the funnel plot, and an asymmetric plot suggested possible publication bias.

RESULTS: Twenty-three studies with a total of 1279 HCC patients and 547 healthy volunteers as controls were enrolled. The frequency of circulating Tregs in HCC patients was 87% higher than in healthy controls (OR = 1.87, 95%CI: 1.49-2.34). The frequency of Tregs in the HCC tumor microenvironment was significantly higher than that in tumor-surrounding tissue and biopsy specimens from healthy livers (OR = 4.04, 95%CI: 2.10-7.79, P = 0.000; OR = 2.869, 95%CI: 2.16-3.82, P = 0.000). However, subgroup analyses based on the different types of tumors or patient characteristics such as tumor size, tumor number or α fetoprotein (AFP) levels in HCC patients, showed that populations of Tregs as a whole were not significantly changed between groups (P > 0.05 for all).

CONCLUSION: There is an obvious association between Tregs and pathogenesis of HCC. Further well-designed clinical studies are warranted to illustrate the potential role of Tregs in HCC.

Keywords: Hepatocellular carcinoma, Regulatory T cells, Meta-analysis, Tumor escape, Cellular immunity

Core tip: Association of increased populations of regulatory T cells (Tregs) with impaired immune response in hepatocellular carcinoma (HCC) patients has been proposed. This study systematically quantified the strength of this association by meta-analysis. The available literature revealed that HCC patients have more Tregs in the circulation and tumor tissue. However, more well-designed clinical studies are needed to investigate further the potential role of Tregs in the pathogenesis of HCC, because subgroup analyses based on other tumors or patient characteristics did not show any positive correlation between Tregs and such pathological states.