Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer

ABSTRACT

Objective: This study was conducted to explore the prognostic value of the methylation status of the ASC/ TMS1 (apoptosis-associated speck-like protein containing a CARD/the target of methylation-induced silencing-1) promoter in gastric cancer (GC). Methods: ASC/TMS1 expression was detected in GC tissues and normal gastric mucosal tissues by real-time quantitative PCR and Western blot analysis. Methylationspecific PCR (MSP) analysis was performed to detect the methylated degrees of the DNA of the ASC/TMS1 promoter of 200 GC patients. Associations between molecular, clinicopathological characteristics and survival data were analyzed. Results: The mRNA and protein expression levels of ASC/TMS1 in GC tissues were lower than those in normal gastric mucosal tissues. With the MSP detection, ASC/ TMS1 promoter methylation was found in 68 (34 %) in 200 GC tissues, while none of 40 normal gastric mucosal tissues were found to be methylated. The size of primary tumor and lymph node metastasis were identified as independent relative factors of methylation status of the ASC/ TMS1 promoter in GC tissues. Multivariate analysis results demonstrated that the degree of differentiation, serosal invasion, lymph node metastasis and methylated status of ASC/TMS1 promoter were independent prognostic indicators of GC. Lymph node metastasis and methylated status of ASC/TMS1 promoter were optimal prognostic predictors of GC patients, as identified by Cox regression with Akaike information criterion value calculation. Conclusions: The methylated status of ASC/TMS1 promoter had the potential applicability for clinical evaluation the prognosis of GC (AU)

RESUMEN

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