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

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. 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. 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. 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.

Kanda M ，Shimizu D ，Nomoto S ，Hibino S ，Oya H ，Takami H ，Kobayashi D ，Yamada S ，Inokawa Y ，Tanaka C ，Fujii T ，Sugimoto H ，Koike M ，Fujiwara M ，Kodera Y ... -  《-》

Identification of intragenic methylation in the TUSC1 gene as a novel prognostic marker of hepatocellular carcinoma.

Shimizu D ，Kanda M ，Nomoto S ，Oya H ，Takami H ，Hibino S ，Suenaga M ，Inokawa Y ，Hishida M ，Takano N ，Nishikawa Y ，Yamada S ，Fujii T ，Nakayama G ，Sugimoto H ，Koike M ，Fujiwara M ，Kodera Y ... -  《-》

Prognostic impact of expression and methylation status of DENN/MADD domain-containing protein 2D in gastric cancer.

Kanda M ，Shimizu D ，Nomoto S ，Takami H ，Hibino S ，Oya H ，Hashimoto R ，Suenaga M ，Inokawa Y ，Kobayashi D ，Tanaka C ，Yamada S ，Fujii T ，Nakayama G ，Sugimoto H ，Koike M ，Fujiwara M ，Kodera Y ... -  《-》

Epigenetic inactivation of BCL6B, a novel functional tumour suppressor for gastric cancer, is associated with poor survival.

Xu L ，Li X ，Chu ES ，Zhao G ，Go MY ，Tao Q ，Jin H ，Zeng Z ，Sung JJ ，Yu J ... -  《-》

Clinical significance of the methylated cytosine-phosphate-guanine sites of protocadherin-10 promoter for evaluating the prognosis of gastric cancer.

Protocadherin-10 (PCDH10) has been identified as a tumor suppressor gene in multiple carcinomas. In this study, we intended to elucidate the clinical applicability of the methylation of CpG sites of PCDH10 promoter for prognostic prediction in gastric cancer (GC). Qualitative and quantitative detections of PCDH10 promoter methylation were performed with methylation-specific polymerase chain reaction (MSP) and bisulphite genomic sequencing, respectively. The methylated statuses of 27 cytosine-phosphate-guanine (CpG) sites in PCDH10 promoter were detected in a series of 458 GC tissues to supply precise information of prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed. Protocadherin-10 promoter methylation was found in 91.92% in all patients. Gastric cancer patients with 5 or more methylated CpG sites of PCDH10 promoter was significantly associated with poorer survival (p = 0.038). Meanwhile, methylation of combined CpG (-115, -108, -13, and +3) sites was also identified to provide elaborate survival discrimination for GC patients (p = 0.044). On multivariate survival analysis, methylation of combined CpG (-115, -108, -13, and +3) sites (hazard ratio [HR] = 1.255; p = 0.049) was identified to be an independent prognostic indicator of GC, as were N stage and T stage. Additionally, the methylation of combined CpG (-115, -108, -13, and +3) sites had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other 2 independent predictors of the survival. Ultimately, we demonstrated that the methylation of combined CpG (-115, -108, -13, and +3) sites was negatively associated with PCDH10 expression in GC tissues. The methylated CpG sites of PCDH10 promoter had significant applicability for clinical evaluation of the prognosis of GC.

Deng J ，Liang H ，Ying G ，Dong Q ，Zhang L ，Yu J ，Fan D ，Hao X ... -  《-》