Meta-Analysis
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World J Gastroenterol. Nov 7, 2013; 19(41): 7189-7196
Published online Nov 7, 2013. doi: 10.3748/wjg.v19.i41.7189
Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: A meta-analysis
Ze-Hua Zhao, Yu-Chen Fan, Yang Yang, Kai Wang
Ze-Hua Zhao, Yu-Chen Fan, Yang Yang, Kai Wang, Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Yu-Chen Fan, Kai Wang, Institute of Hepatology, Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Zhao ZH and Wang K designed research; Zhao ZH and Fan YC performed the research and analyzed the data; Zhao ZH, Fan YC and Yang Y wrote the paper; Wang K supervised the whole study.
Supported by Key Project of Chinese Ministry of Science and Technology, No. 2012ZX10002007 and No. 2013ZX10002001; National Natural Science Foundation of China, No. 81171579 and No. 81201287; Natural Science Foundation of Shandong Province, China, No. ZR2010HM070 and No. ZR2010HQ040
Correspondence to: Kai Wang, MD, PhD, Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan 250012, China. wangdoc876@126.com
Telephone: +86-531-86630809 Fax: +86-531-86927544
Received: July 14, 2013
Revised: August 15, 2013
Accepted: August 20, 2013
Published online: November 7, 2013
Processing time: 124 Days and 21.4 Hours
Abstract

AIM: To assess diagnostic accuracy of Ras association domain family 1A (RASSF1A) promoter methylation in body fluids (serum, plasma and whole blood) for hepatocellular carcinoma (HCC).

METHODS: Relative information about study characteristics and incidence of RASSF1A methylation was collected. Quality of all included studies was evaluated by Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity were pooled using a random-effect model, and a summary receiver operating characteristic curve was used to demonstrate the overall diagnostic performance. Positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) with 95%CI were also calculated. Meta-regression was applied to analyze observed heterogeneity, and Deeks’ test was performed to detect publication bias.

RESULTS: After a systematic literature review, seven studies with a total of 302 cases of HCC and 250 cases of chronic liver diseases were included in the analysis. The pooled sensitivity and specificity were 0.70 (95%CI: 0.49-0.85) and 0.72 (95%CI: 0.54-0.85), respectively. The PLR was 2.51 (95%CI: 1.64-3.86), NLR was 0.41 (95%CI: 0.25-0.68), and DOR was 6.13 (95%CI: 3.17-11.84). The χ2 values of sensitivity, specificity, PLR, NLR and DOR were 59.41 (P < 0.001), 50.50 (P < 0.001), 17.40 (P = 0.010), 31.24 (P < 0.001) and 80.51 (P < 0.001), respectively. The area under the curve was 0.77 (95%CI: 0.73-0.81). Three factors were analyzed by univariate meta-regression and none was significant to interpret the observed heterogeneity (P > 0.05). No significant publication bias was detected by Deeks’ test (P = 0.346).

CONCLUSION: We showed the potential diagnostic value of RASSF1A methylation in body fluids in HCC patients and it may improve diagnostic accuracy combined with the α-fetoprotein test.

Keywords: Methylation; Ras association domain family 1A; Hepatocellular carcinoma; Biomarker; Diagnostic sensitivity; Diagnostic specificity

Core tip: The published results on the diagnostic potential of Ras association domain family 1A (RASSF1A) promoter methylation for detection of hepatocellular carcinoma (HCC) are not consistent. We performed a comprehensive literature search to assess the diagnostic accuracy of RASSF1A promoter methylation. We rigorously selected patients with chronic liver diseases as controls to mimic clinical practice, and we only included studies that used body fluids as samples for detection because such an approach is non-invasive and promising for clinical application. Our meta-analysis demonstrated good sensitivity and specificity of RASSF1A methylation and may complement the α-fetoprotein test to improve HCC detection.