Jingyu Deng1, Han Liang1, Rupeng Zhang1, Guoguang Ying2, Xingmin Xie1, Jun Yu3, Daiming Fan4, Xishan Hao1. 1. Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer Tianjin, China. 2. Central Laboratory, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer Tianjin, China. 3. Institute of Digestive Disease, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong Shatin, Hong Kong. 4. State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University Xi'an China.
Abstract
OBJECTIVE: To elucidate the clinical significance of the methylated status of CpG sites of dapper homolog 1 (DACT1) promoter in the survival prediction in gastric cancer (GC). METHODS: The large scale GC patients (n=459) were analyzed for the quantitatively methylated status of CpG sites of DACT1 DNA promoter with the bisulphite sequencing PCR (BSP). With gene sequencing analysis, the methylated statuses of 12 cytosine-phosphate-guanine (CpG) sites in DACT1 promoter were detected to supply detailed information for the precisely prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed. RESULTS: With the MSP detection, different methylated levels of DACT1 promoter were identified in the 25 GC tissues, while none of 25 normal gastric mucosal tissues were found to be methylated. DACT1 promoter methylation was found in 28.32% in 459 patients. GC patients with 4 or more methylated CpG sites of DACT1 promoter was significantly associated with the poorer survival (P=0.19). The methylated statuses of CpG -515, CpG -435, and CpG -430 sites were also identified to provide the elaborate survival discrimination for 459 GC patients, respectively (P=0.049, =0.006, and =0.037). In addition, we demonstrated that the methylated CpG site count had smallest AIC and BIC values than other three methylated status of CpG sites for prediction the survival of 459 GC patients. CONCLUSIONS: The methylated CpG site count of DACT1 promoter had the significant applicability for clinical evaluation the prognosis of GC.
OBJECTIVE: To elucidate the clinical significance of the methylated status of CpG sites of dapper homolog 1 (DACT1) promoter in the survival prediction in gastric cancer (GC). METHODS: The large scale GC patients (n=459) were analyzed for the quantitatively methylated status of CpG sites of DACT1 DNA promoter with the bisulphite sequencing PCR (BSP). With gene sequencing analysis, the methylated statuses of 12 cytosine-phosphate-guanine (CpG) sites in DACT1 promoter were detected to supply detailed information for the precisely prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed. RESULTS: With the MSP detection, different methylated levels of DACT1 promoter were identified in the 25 GC tissues, while none of 25 normal gastric mucosal tissues were found to be methylated. DACT1 promoter methylation was found in 28.32% in 459 patients. GC patients with 4 or more methylated CpG sites of DACT1 promoter was significantly associated with the poorer survival (P=0.19). The methylated statuses of CpG -515, CpG -435, and CpG -430 sites were also identified to provide the elaborate survival discrimination for 459 GC patients, respectively (P=0.049, =0.006, and =0.037). In addition, we demonstrated that the methylated CpG site count had smallest AIC and BIC values than other three methylated status of CpG sites for prediction the survival of 459 GC patients. CONCLUSIONS: The methylated CpG site count of DACT1 promoter had the significant applicability for clinical evaluation the prognosis of GC.
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