Hypermethylation of the RECK gene predicts poor prognosis in oral squamous cell carcinomas.
The RECK gene is a novel tumor suppressor gene that regulates matrix metalloproteinases (MMPs) to inhibit tumor angiogenesis, invasion and metastasis. We investigated the methylation status of the RECK gene in 40 primary oral squamous cell carcinomas (OSCC) and 20 paired adjacent normal mucosa by methylation-specific PCR. Furthermore, we determined the prognostic importance of RECK hypermethylation in OSCC patients. Our findings showed that the RECK gene was methylated in 52.5% (21 of 40) of the primary OSCC. Among the 20 cases with corresponding normal tissues, RECK hypermethylation was detected in both primary tumor (55%, 11 of 20) and adjacent normal mucosa (30%, 6 of 20). Methylation of the RECK gene was not detected in all normal oral mucosa samples of the 12 healthy controls. In univariate analysis, RECK hypermethylation was inversely correlated with recurrence-free survival (p=0.027) and overall survival (p=0.023) of the OSCC patients. Multivariate analysis showed that the methylation status of the RECK gene was the only independent prognostic factor affecting overall survival (p=0.037). The result indicates that hypermethylation of RECK promoter is a common event in human OSCC, occurs concurrently in tumor-adjacent normal mucosa and is correlated with poor prognosis in OSCC patients. Although additional work is needed, hypermethylation of the RECK gene is a promising biomarker in early detection and prognosis for oral cancer patients.
Long
Nguyen Khanh
NK
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. longnk76@yahoo.com
Kato
Keizo
K
Yamashita
Tomomi
T
Makita
Hiroki
H
Toida
Makoto
M
Hatakeyama
Daijiro
D
Hara
Akira
A
Mori
Hideki
H
Shibata
Toshiyuki
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D058851:GPI-Linked Proteins; D016147:Genes, Tumor Suppressor; D006801:Humans; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics*; D011379:Prognosis
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human