title: PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma.
abstract: PGP9.5/UCHL1 is a member of the carboxyl-terminal ubiquitin hydrolase family with a potential role in carcinogenesis. We previously identified PGP9.5 as a putative tumor-suppressor gene and methylation of the promoter as a cancer-specific event in primary cancer tissues. In this current study, we analyzed PGP9.5 methylation in 50 esophageal squamous cell carcinoma (ESCC) primary tumors with well characterized clinicopathologic variables including patient outcome. Two independent modalities for methylation analysis (TaqMan methylation-specific PCR and combined bisulfite restriction analysis) were used to analyze these samples. The two data sets were consistent with each other, as the 21 patients (42%) with highest methylation levels by TaqMan analysis all showed visible combined bisulfite restriction analysis bands on acrylamide gels. Using an optimized cutoff value by TaqMan quantitation, we found that patients with higher PGP9.5 methylation ratios in the primary tumor showed poorer 5-year survival rates than those without PGP9.5 methylation (P = 0.01). A significant correlation was also seen between PGP9.5 promoter methylation and the presence of regional lymph node metastases (P = 0.03). Multivariate analysis subsequently revealed that PGP9.5 methylation was an independent prognostic factor for ESCC survival (P = 0.03). These results suggest that PGP9.5 promoter methylation could be a clinically applicable marker for ESCC progression.
authors.affiliation: Department of Otolaryngology, Head and Neck Cancer Research, Johns Hopkins University, Baltimore, Maryland 21205-2196, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Mandelker
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokumaru
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: David L
authors.initials: DL
authors.lastname: Howard
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Andre Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Jiang
authors.forename: Hannah Lui
authors.initials: HL
authors.lastname: Park
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Motonobu
authors.initials: M
authors.lastname: Osada
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm