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Poor survival is associated with the methylated degree of zinc-finger protein 545 (ZNF545) DNA promoter in gastric cancer.

Deng J, Liang H, Ying G, Dong Q, Zhang R, Yu J, Fan D, Hao X - Oncotarget (2015)

Bottom Line: Zinc-finger protein 545 (ZNF545) was identified as a gastric tumour suppressor and potentially independent prognostic factor.In the methylation-specific PCR (MSP) analysis cohort, we found that GC patients with hypermethylated ZNF545 promoter exhibited significantly shorter median OS than those with unmethylated ZNF545 promoter and those with hypomethylated ZNF545 promoter.These findings indicated that the methylated CpG sites of the ZNF545 promoter could be used for the clinical prediction of the prognosis of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.

ABSTRACT
Zinc-finger protein 545 (ZNF545) was identified as a gastric tumour suppressor and potentially independent prognostic factor. At the present study, we found that lower expression of ZNF545 was specific in gastric cancer (GC) tissues, and the inconsistently methylated levels of ZNF545 promoter were identified in the gastric cancer tissues. In the methylation-specific PCR (MSP) analysis cohort, we found that GC patients with hypermethylated ZNF545 promoter exhibited significantly shorter median OS than those with unmethylated ZNF545 promoter and those with hypomethylated ZNF545 promoter. In the other cohort, we also demonstrated that GC patients with three or more methylated CpG sites in the ZNF545 promoter were significantly associated with poor survival by using the bisulphite gene sequencing (BGS). The methylated degrees of five CpG sites (-232, -214, -176, -144 and -116) could also provide distinct survival discrimination of patients with GC. These findings indicated that the methylated CpG sites of the ZNF545 promoter could be used for the clinical prediction of the prognosis of GC.

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Kaplan-Meier survival curves comparing months of survival in gastric cancer patients are shown for (A) methylated statuses of ZNF545 promoter (MSP), (B) methylated CpG site count of ZNF545 promoter, (C) methylated status of CpG −232, (D) methylated status of CpG −214, (E) methylated status of CpG −176, (F) methylated status of CpG −144, and (G) methylated status of CpG −116.
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Figure 4: Kaplan-Meier survival curves comparing months of survival in gastric cancer patients are shown for (A) methylated statuses of ZNF545 promoter (MSP), (B) methylated CpG site count of ZNF545 promoter, (C) methylated status of CpG −232, (D) methylated status of CpG −214, (E) methylated status of CpG −176, (F) methylated status of CpG −144, and (G) methylated status of CpG −116.

Mentions: In univariate survival analysis, four clinicopathological characteristics were significantly associated with the survival of 300 patients with GC. In MSP analysis, methylated ZNF545 promoter was observed in the same patients. The following characteristics were observed (Table 2): T stage (P < 0.001); N stage (P < 0.001); location of lymph node metastasis (P < 0.001); and gender (P = 0.048). Although the methylation of the ZNF545 promoter was significantly associated with the OS of patients, as indicated in Kaplan-Meier curves (P < 0.001; Table 2; Figure 4), no statistical survival difference was found between 61 patients with hypomethylated ZNF545 promoter and 167 patients with unmethylated ZNF545 promoter (P = 0.373). These factors were included in a multivariate Cox proportional hazard model to adjust the effects of covariates. N stage (HR = 1.520, P < 0.001) and T stage (HR = 1.432, P = 0.001) were identified as the independent predictors of the OS of patients with GC rather than ZNF545 promoter methylation, as revealed by the multivariate survival analysis (Table 2).


Poor survival is associated with the methylated degree of zinc-finger protein 545 (ZNF545) DNA promoter in gastric cancer.

Deng J, Liang H, Ying G, Dong Q, Zhang R, Yu J, Fan D, Hao X - Oncotarget (2015)

Kaplan-Meier survival curves comparing months of survival in gastric cancer patients are shown for (A) methylated statuses of ZNF545 promoter (MSP), (B) methylated CpG site count of ZNF545 promoter, (C) methylated status of CpG −232, (D) methylated status of CpG −214, (E) methylated status of CpG −176, (F) methylated status of CpG −144, and (G) methylated status of CpG −116.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414205&req=5

Figure 4: Kaplan-Meier survival curves comparing months of survival in gastric cancer patients are shown for (A) methylated statuses of ZNF545 promoter (MSP), (B) methylated CpG site count of ZNF545 promoter, (C) methylated status of CpG −232, (D) methylated status of CpG −214, (E) methylated status of CpG −176, (F) methylated status of CpG −144, and (G) methylated status of CpG −116.
Mentions: In univariate survival analysis, four clinicopathological characteristics were significantly associated with the survival of 300 patients with GC. In MSP analysis, methylated ZNF545 promoter was observed in the same patients. The following characteristics were observed (Table 2): T stage (P < 0.001); N stage (P < 0.001); location of lymph node metastasis (P < 0.001); and gender (P = 0.048). Although the methylation of the ZNF545 promoter was significantly associated with the OS of patients, as indicated in Kaplan-Meier curves (P < 0.001; Table 2; Figure 4), no statistical survival difference was found between 61 patients with hypomethylated ZNF545 promoter and 167 patients with unmethylated ZNF545 promoter (P = 0.373). These factors were included in a multivariate Cox proportional hazard model to adjust the effects of covariates. N stage (HR = 1.520, P < 0.001) and T stage (HR = 1.432, P = 0.001) were identified as the independent predictors of the OS of patients with GC rather than ZNF545 promoter methylation, as revealed by the multivariate survival analysis (Table 2).

Bottom Line: Zinc-finger protein 545 (ZNF545) was identified as a gastric tumour suppressor and potentially independent prognostic factor.In the methylation-specific PCR (MSP) analysis cohort, we found that GC patients with hypermethylated ZNF545 promoter exhibited significantly shorter median OS than those with unmethylated ZNF545 promoter and those with hypomethylated ZNF545 promoter.These findings indicated that the methylated CpG sites of the ZNF545 promoter could be used for the clinical prediction of the prognosis of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.

ABSTRACT
Zinc-finger protein 545 (ZNF545) was identified as a gastric tumour suppressor and potentially independent prognostic factor. At the present study, we found that lower expression of ZNF545 was specific in gastric cancer (GC) tissues, and the inconsistently methylated levels of ZNF545 promoter were identified in the gastric cancer tissues. In the methylation-specific PCR (MSP) analysis cohort, we found that GC patients with hypermethylated ZNF545 promoter exhibited significantly shorter median OS than those with unmethylated ZNF545 promoter and those with hypomethylated ZNF545 promoter. In the other cohort, we also demonstrated that GC patients with three or more methylated CpG sites in the ZNF545 promoter were significantly associated with poor survival by using the bisulphite gene sequencing (BGS). The methylated degrees of five CpG sites (-232, -214, -176, -144 and -116) could also provide distinct survival discrimination of patients with GC. These findings indicated that the methylated CpG sites of the ZNF545 promoter could be used for the clinical prediction of the prognosis of GC.

Show MeSH
Related in: MedlinePlus