Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2019; 11(10): 909-924
Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.909
Abnormally expressed circular RNAs as novel non-invasive biomarkers for hepatocellular carcinoma: A meta-analysis
Ya-Lin Jiang, Meng-Meng Shang, Shi-Zhen Dong, Yong-Chao Chang
Ya-Lin Jiang, Meng-Meng Shang, Shi-Zhen Dong, Yong-Chao Chang, Department of Clinical Laboratory, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China
Meng-Meng Shang, Department of Clinical Laboratory, The Family Planning Guidance Station of Luanchuan County, Luoyang 471500, Henan Province, China
Author contributions: Jiang YL acquired, analyzed, and interpreted the data and drafted, revised, and finally approved the article; Shang MM and Dong SZ acquired, analyzed, and interpreted the data and finally approved the article; Chang YC conceived and designed the study and critically revised and finally approved the article.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Yong-Chao Chang, MD, PhD, Professor, Department of Clinical Laboratory, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 24, Jinghua Road, Jianxi District, Luoyang 471003, Henan Province, China. zero6666888@163.com
Telephone: +86-379-64830723 Fax: +86-379-64830723
Received: June 13, 2019
Peer-review started: June 19, 2019
First decision: July 31, 2019
Revised: August 6, 2019
Accepted: September 4, 2019
Article in press: September 4, 2019
Published online: October 15, 2019
Abstract
BACKGROUND

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that may have roles in cancer genesis and development. In the recent literature, dysregulated circRNAs have been extensively investigated in hepatocellular carcinoma (HCC). Whether or not circRNAs are of clinical value for the management of HCC has not been characterized.

AIM

To meta-analyze the diagnostic and prognostic value of abnormally expressed circRNAs in HCC.

METHODS

Eligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients’ clinical characteristics, including diagnostic efficacy and overall survival, were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on Stata 12.0. The trim and fill method was adopted to assess the possible effects from publication bias.

RESULTS

A total of 21 eligible studies were included. The pooled sensitivity, specificity, and area under the curve of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were 0.78 (95%CI: 0.69–0.85), 0.80 (95%CI: 0.74–0.86), and 0.86, respectively. Survival analyses showed that the down-regulated circRNA expression signature correlated perfectly with HCC survival [hazard ratio (HR) = 0.42, 95%CI: 0.19–0.91, P = 0.028; I2 = 92.7%, P = 0.000], whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95%CI: 1.50–3.30, P = 0.000; I2 = 91%, P = 0.000). Moreover, abnormally expressed circRNAs were intimately associated with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum alpha fetal protein level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results.

CONCLUSION

Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) for HCC diagnosis and prognosis.

Keywords: CircRNA, Hepatocellular carcinoma, Diagnosis, Prognosis, Meta-analysis

Core tip: Current studies investigating the clinical significance of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC) were conducted using single-center and small-scale design, and the findings were controversial. We collected and analyzed the up-to-date clinical data on the significance of circRNAs in the diagnosis and prognosis of HCC. The results indicated that circRNAs may be novel indicators for the prognosis and diagnosis of HCC.