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Zic1 Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric Cancer and Intraepithelial Neoplasia.

Chen X, Lin Z, Xue M, Si J, Chen S - PLoS ONE (2015)

Bottom Line: Methylation status in the GC group was not significantly associated with tumor size, tumor differentiation, lymph node metastasis, TNM staging, or tumor invasion (p > 0.05).Assessment of the significance of detection of the carcino-embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis revealed that the sensitivity of Zic1 promoter methylation was significantly higher than that of the CEA level as a marker and that the combined measurement of these two indices (parallel testing) improved sensitivity.Taken together, our results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
Gastric cancer (GC) remains one of the most common digestive cancers worldwide; however, most patients present at an advanced stage at initial diagnosis. Zic1 is a novel candidate tumor suppressor gene that is epigenetically silenced in GC. In this study, we investigated Zic1 promoter methylation in plasma DNA as a novel molecular marker for the early diagnosis and monitoring of GC. Methylation-specific polymerase chain reaction (MSP) assay was performed to detect Zic1 promoter methylation in plasma DNA from 20 healthy subjects, 50 gastric intraepithelial neoplasia patients, and 104 GC patients. The Zic1 promoter methylation rate in the plasma samples from the healthy control group was 0%, but it reached 54.0% in the intraepithelial neoplasia group and 60.6% in the GC group. The latter two values were significantly higher than that found in the healthy control group (p < 0.05), with a 100% specificity for intraepithelial neoplasia and GC diagnosis. The positive predictive value of plasma Zic1 promoter methylation for the diagnosis of intraepithelial neoplasia and GC was 100%. Methylation status in the GC group was not significantly associated with tumor size, tumor differentiation, lymph node metastasis, TNM staging, or tumor invasion (p > 0.05). Assessment of the significance of detection of the carcino-embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis revealed that the sensitivity of Zic1 promoter methylation was significantly higher than that of the CEA level as a marker and that the combined measurement of these two indices (parallel testing) improved sensitivity. Taken together, our results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis. Zic1 promoter methylation may serve as a novel non-invasive plasma biomarker for the early detection of GC and for risk assessment in high-risk populations. The combined measurement of the Zic1 promoter methylation rate and CEA level (parallel testing) may enhance the current guidelines for the early diagnosis of GC.

No MeSH data available.


Related in: MedlinePlus

Percentage of Zic1 promoter methylation in the gastric cancer (GC), gastric intraepithelial neoplasia (GIN), early gastric cancer (ECG) and normal control (NC) groups.The percentages of Zic1 promoter methylation were 60.6% (63/104) in the GC, 54.0% (27/50) in the GIN, 54.8% (17/31) in the EGC and 0.0% (0/20) in the NC groups (*: p < 0.001).
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pone.0133906.g001: Percentage of Zic1 promoter methylation in the gastric cancer (GC), gastric intraepithelial neoplasia (GIN), early gastric cancer (ECG) and normal control (NC) groups.The percentages of Zic1 promoter methylation were 60.6% (63/104) in the GC, 54.0% (27/50) in the GIN, 54.8% (17/31) in the EGC and 0.0% (0/20) in the NC groups (*: p < 0.001).

Mentions: To assess alterations in Zic1 promoter methylation in GC, we first detected the methylation status of this promoter in 104 patients with GC, 50 with GIN, 31 with EGC and 20 NCs and performed comparisons among the groups. The methylation rates of the Zic1 promoter in the plasma samples were 0% in the NC group (0%), increasing to 54.0% in the GIN group and to 60.6% in the GC group (p < 0.001 for both GIN and GC vs. NC), with 100% specificity for GPI diagnosis (20/20) (Fig 1). The positive and negative predictive values and positive and negative likelihood ratios for diagnosing IN and GC were 100% (90/90), 23.8% (20/84), infinite and 0.42, respectively. Representative MSP assay results for Zic1 promoter methylation are shown in Fig 2.


Zic1 Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric Cancer and Intraepithelial Neoplasia.

Chen X, Lin Z, Xue M, Si J, Chen S - PLoS ONE (2015)

Percentage of Zic1 promoter methylation in the gastric cancer (GC), gastric intraepithelial neoplasia (GIN), early gastric cancer (ECG) and normal control (NC) groups.The percentages of Zic1 promoter methylation were 60.6% (63/104) in the GC, 54.0% (27/50) in the GIN, 54.8% (17/31) in the EGC and 0.0% (0/20) in the NC groups (*: p < 0.001).
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pone.0133906.g001: Percentage of Zic1 promoter methylation in the gastric cancer (GC), gastric intraepithelial neoplasia (GIN), early gastric cancer (ECG) and normal control (NC) groups.The percentages of Zic1 promoter methylation were 60.6% (63/104) in the GC, 54.0% (27/50) in the GIN, 54.8% (17/31) in the EGC and 0.0% (0/20) in the NC groups (*: p < 0.001).
Mentions: To assess alterations in Zic1 promoter methylation in GC, we first detected the methylation status of this promoter in 104 patients with GC, 50 with GIN, 31 with EGC and 20 NCs and performed comparisons among the groups. The methylation rates of the Zic1 promoter in the plasma samples were 0% in the NC group (0%), increasing to 54.0% in the GIN group and to 60.6% in the GC group (p < 0.001 for both GIN and GC vs. NC), with 100% specificity for GPI diagnosis (20/20) (Fig 1). The positive and negative predictive values and positive and negative likelihood ratios for diagnosing IN and GC were 100% (90/90), 23.8% (20/84), infinite and 0.42, respectively. Representative MSP assay results for Zic1 promoter methylation are shown in Fig 2.

Bottom Line: Methylation status in the GC group was not significantly associated with tumor size, tumor differentiation, lymph node metastasis, TNM staging, or tumor invasion (p > 0.05).Assessment of the significance of detection of the carcino-embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis revealed that the sensitivity of Zic1 promoter methylation was significantly higher than that of the CEA level as a marker and that the combined measurement of these two indices (parallel testing) improved sensitivity.Taken together, our results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, China.

ABSTRACT
Gastric cancer (GC) remains one of the most common digestive cancers worldwide; however, most patients present at an advanced stage at initial diagnosis. Zic1 is a novel candidate tumor suppressor gene that is epigenetically silenced in GC. In this study, we investigated Zic1 promoter methylation in plasma DNA as a novel molecular marker for the early diagnosis and monitoring of GC. Methylation-specific polymerase chain reaction (MSP) assay was performed to detect Zic1 promoter methylation in plasma DNA from 20 healthy subjects, 50 gastric intraepithelial neoplasia patients, and 104 GC patients. The Zic1 promoter methylation rate in the plasma samples from the healthy control group was 0%, but it reached 54.0% in the intraepithelial neoplasia group and 60.6% in the GC group. The latter two values were significantly higher than that found in the healthy control group (p < 0.05), with a 100% specificity for intraepithelial neoplasia and GC diagnosis. The positive predictive value of plasma Zic1 promoter methylation for the diagnosis of intraepithelial neoplasia and GC was 100%. Methylation status in the GC group was not significantly associated with tumor size, tumor differentiation, lymph node metastasis, TNM staging, or tumor invasion (p > 0.05). Assessment of the significance of detection of the carcino-embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis revealed that the sensitivity of Zic1 promoter methylation was significantly higher than that of the CEA level as a marker and that the combined measurement of these two indices (parallel testing) improved sensitivity. Taken together, our results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis. Zic1 promoter methylation may serve as a novel non-invasive plasma biomarker for the early detection of GC and for risk assessment in high-risk populations. The combined measurement of the Zic1 promoter methylation rate and CEA level (parallel testing) may enhance the current guidelines for the early diagnosis of GC.

No MeSH data available.


Related in: MedlinePlus