Association between Ras association domain family 1A promoter methylation and hepatocellular carcinoma: a meta-analysis.
OBJECTIVE
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 χ(2) 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).


CONCLUSIONS
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.
Ze-Hua Zhao, Yu-Chen Fan, Yang Yang, Kai Wang, Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.
Ze-Hua
ZH
Zhao
Yu-Chen
YC
Fan
Yang
Y
Yang
Kai
K
Wang
D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D019175:DNA Methylation; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D016013:Likelihood Functions; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000032:analysis
C097353:AFP protein, human; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000509:alpha-Fetoproteins
Biomarker; Diagnostic sensitivity; Diagnostic specificity; Hepatocellular carcinoma; Methylation; Ras association domain family 1A