Frequent promoter methylation of M-cadherin in hepatocellular carcinoma is associated with poor prognosis.
BACKGROUND
Many cadherins (CDH) are associated with various types of cancer and their genetic and epigenetic alterations might be involved in carcinogenesis.


METHODS
We examined the methylation status of CDH genes in primary hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues derived from 47 patients, and evaluated the correlation with clinicopathological parameters.


RESULTS
Hypermethylation was detected at a ratio ranging from 0% to 55.3%. In particular, M-cadherin (CDH15) was the most hypermethylated of 7 CDH genes. Patients with methylated M-cadherin had shorter 5-year survival rates than patients with unmethylated M-cadherin (overall survival rates, 67.4% vs. 82.7%; p = 0.0167) when assessed using Kaplan-Meier curves. Multivariate analysis revealed that M-cadherin methylation status was an independent predictor of survival.


CONCLUSIONS
We found that M-cadherin methylation status has prognostic significance for the poorer survival of patients with HCC. This is the first definitive report of a correlation between M-cadherin and the prognosis of patients with HCC.
Yamada
Suguru
S
Department of Surgery II, Graduate School and Faculty of Medicine, University of Nagoya, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. suguru@med.nagoya-u.ac.jp
Nomoto
Shuji
S
Fujii
Tsutomu
T
Takeda
Shin
S
Kanazumi
Naohito
N
Sugimoto
Hiroyuki
H
Nakao
Akimasa
A
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D015820:Cadherins; D012333:RNA, Messenger; C070896:M-cadherin