Clinicopathological and prognostic significance of CDH1 hypermethylation in hepatocellular carcinoma: a meta-analysis

Figures & data

Figure 1 Schematic flow diagram for selection of included studies.

Table 1 Main characteristics of included studies

Authors	Year	Country	Histology (M/T)			Grade (M/T)		Stage (M/T)		Methods
			NLT	CLD	HCC	L	H	I/II	III/IV
Zekri et al^Citation35	2014	Egypt	2/13	7/38	17/31					MSP
Herath et al^Citation36	2009	Australia	2/20		14/61					MSP
Nishida et al^Citation37	2008	Japan	4/22		21/77					COBRA
Katoh et al^Citation38	2006	Japan			26/60	16/32	10/28	20/42	6/18	MSP
Yuan et al^Citation39	2006	China			30/112			20/73	10/39	MSP
Kwon et al^Citation40	2005	Korea		1/13	32/64	25/52	7/12	28/56	4/8	MSP
Herath et al^Citation41	2004	South Africa	2/20		14/50					MSP
Schagdarsurengin et al^Citation26	2003	Germany	0/2		2/15					MSP
Lee et al^Citation42	2003	Korea	4/60	2/30	20/60					MSP
Yang et al^Citation18	2003	USA	1/14	3/15	25/51					MSP
Matsumura et al^Citation43	2001	Japan	1/30		7/30	7/26	1/4			Southern blot
Kanai et al^Citation25	1997	Japan		11/24	16/24					Southern blot

Abbreviations: CLD, chronic liver disease; COBRA, combined bisulfite restriction analysis; H, high grade; HCC, hepatocellular carcinoma; L, low grade; M, methylation number; MSP, methylation-specific PCR; NLT, normal liver tissue; T, total number.

Figure 2 Forest plot for CDH1 promoter hypermethylation in HCC and normal liver tissue.

Notes: The squares represent the weight of individual study in the meta-analysis and the line width indicates the corresponding 95% CI. The diamond represents the pooled OR and the width of diamond indicates 95% CI.

Abbreviations: HCC, hepatocellular carcinoma; NLT, normal liver tissue; M–H, Mantel–Haenszel.

Figure 3 Forest plot for CDH1 promoter hypermethylation in HCC and CLD.

Notes: The squares represent the weight of individual study in the meta-analysis and the line width indicates the corresponding 95% CI. The diamond represents the pooled OR and the width of diamond indicates 95% CI.

Abbreviations: CLD, chronic liver disease; HCC, hepatocellular carcinoma; M–H, Mantel–Haenszel.

Figure 4 Forest plot for CDH1 promoter hypermethylation in high and low grade of histological differentiation.

Notes: The squares represent the weight of individual study in the meta-analysis and the line width indicates the corresponding 95% CI. The diamond represents the pooled OR and the width of diamond indicates 95% CI.

Abbreviation: M–H, Mantel–Haenszel.

Figure 5 Forest plot for CDH1 promoter hypermethylation in different stage of HCC.

Notes: The squares represent the weight of individual study in the meta-analysis and the line width indicates the corresponding 95% CI. The diamond represents the pooled OR and the width of diamond indicates 95% CI.

Abbreviations: HCC, hepatocellular carcinoma; M–H, Mantel–Haenszel.

Figure 6 Comparison of overall survival between patients with high and low expression of CDH1 mRNA.

Abbreviation: HR, hazard ratio.

Figure 7 Funnel plot for publication bias.

Notes: (A) CDH1 promoter hypermethylation in HCC and normal liver tissue; (B) CDH1 promoter hypermethylation in HCC and CLD; (C) CDH1 promoter hypermethylation in high and low grade of histological differentiation; (D) CDH1 promoter hypermethylation in different stage of HCC. Area of the circle represents the weight of individual study.

Abbreviations: CLD, chronic liver disease; HCC, hepatocellular carcinoma; SE, standard error.

ZekriARBahnasyAAShoeabFEMethylation of multiple genes in hepatitis C virus associated hepatocellular carcinomaJ Adv Res201451274025685469

 PubMedGoogle Scholar

HerathNIPurdieDMKewMCVarying etiologies lead to different molecular changes in Australian and South African hepatocellular carcinomasInt J Oncol20093551081108919787262

 PubMed Web of Science ®Google Scholar

NishidaNNagasakaTNishimuraTIkaiIBolandCRGoelAAberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinomaHepatology200847390891818161048

 PubMed Web of Science ®Google Scholar

KatohHShibataTKokubuAEpigenetic instability and chromosomal instability in hepatocellular carcinomaAm J Pathol200616841375138416565510

 PubMed Web of Science ®Google Scholar

YuanYWangJLiJFrequent epigenetic inactivation of spleen tyrosine kinase gene in human hepatocellular carcinomaClin Cancer Res200612226687669517121887

 PubMed Web of Science ®Google Scholar

KwonGYYooBCKohKCChoJWParkWSParkCKPromoter methylation of E-cadherin in hepatocellular carcinomas and dysplastic nodulesJ Korean Med Sci200520224224715831995

 PubMed Web of Science ®Google Scholar

HerathNIWalshMDKewMCYoungJLeggettBAMacdonaldGACadherin/catenin complex appears to be intact in hepatocellular carcinomas from Australia and South AfricaJ Gastroenterol Hepatol200419667668215151624

 PubMed Web of Science ®Google Scholar

SchagdarsurenginUWilkensLSteinemannDFrequent epigenetic inactivation of the RASSF1A gene in hepatocellular carcinomaOncogene200322121866187112660822

 PubMed Web of Science ®Google Scholar

LeeSLeeHJKimJHLeeHSJangJJKangGHAberrant CpG island hypermethylation along multistep hepatocarcinogenesisAm J Pathol200316341371137814507645

 PubMed Web of Science ®Google Scholar

YangBGuoMHermanJGClarkDPAberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinomaAm J Pathol200316331101110712937151

 PubMed Web of Science ®Google Scholar

MatsumuraTMakinoRMitamuraKFrequent down-regulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomasClin Cancer Res20017359459911297254

 PubMed Web of Science ®Google Scholar

KanaiYUshijimaSHuiAMThe E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomasInt J Cancer19977133553599139867

 PubMed Web of Science ®Google Scholar