Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer.

BACKGROUND AND OBJECTIVES:The prognosis of advanced gastric cancer (GC) remains dismal. The aim of this study was to identify a novel tumor suppressor gene (TSG) with repressed transcription by aberrant DNA methylation in GC. METHODS:The expression and methylation status of tumor suppressor candidate 1 (TUSC1) were evaluated in GC cell lines and 112 pairs of surgical specimens. TUSC1 protein expression and distribution in GC tissue were determined by immunohistochemistry. RESULTS:The majority of GC cell lines (83%) and GC tissues (82%) showed downregulation of TUSC1 mRNA compared with noncancerous tissues. No significant differences were found in TUSC1 mRNA expression between three GC subtypes categorized by tumor locations and morphology. Reduced expression of TUSC1 mRNA in GC tissues was significantly associated with advanced T stage, vessel invasion and lymph node metastasis, leading to poor prognosis. The expression patterns of TUSC1 protein were confirmed to be consistent with those of TUSC1 mRNA. Sixty-three (57%) of 112 patients showed intragenic hypermethylation of TUSC1 in GC tissues. CONCLUSIONS:Our results suggested that reduced expression of TUSC1 mRNA was related to poor prognosis and TUSC1 is a putative TSG that is suppressed through intragenic hypermethylation in GC.

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