Sensitivity and specificity of markers detected in the gastric cancer (GC) group.

<p>*: <i>Zic1</i> promoter methylation combined with the CEA level (tandem testing)</p><p>/: <i>Zic1</i> promoter methylation combined with the CEA level (parallel testing)</p><p>Sensitivity and specificity of markers detected in the gastric cancer (GC) group.</p

Combined detection of <i>Zic1</i> promoter methylation and the CEA level (parallel testing) in gastric intraepithelial neoplasia (GPI) plasma specimens.

<p>An ROC curve for evaluating the significance of the combined detection of these two parameters for GPI diagnosis.</p

<i>Zic1</i> Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric Cancer and Intraepithelial Neoplasia

<div><p>Gastric cancer (GC) remains one of the most common digestive cancers worldwide; however, most patients present at an advanced stage at initial diagnosis. <i>Zic1</i> is a novel candidate tumor suppressor gene that is epigenetically silenced in GC. In this study, we investigated <i>Zic1</i> 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 <i>Zic1</i> promoter methylation in plasma DNA from 20 healthy subjects, 50 gastric intraepithelial neoplasia patients, and 104 GC patients. The <i>Zic1</i> 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 <i>Zic1</i> 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 <i>Zic1</i> promoter methylation rate for GC diagnosis revealed that the sensitivity of <i>Zic1</i> 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 <i>Zic1</i> promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis. <i>Zic1</i> 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 <i>Zic1</i> promoter methylation rate and CEA level (parallel testing) may enhance the current guidelines for the early diagnosis of GC.</p></div

Percentage of <i>Zic1</i> promoter methylation in the gastric cancer (GC), gastric intraepithelial neoplasia (GIN), early gastric cancer (ECG) and normal control (NC) groups.

<p>The percentages of <i>Zic1</i> 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).</p

Sensitivity and specificity of markers detected in the gastric cancer (GC) group.

<p>*: <i>Zic1</i> promoter methylation combined with the CEA level (tandem testing)</p><p>/: <i>Zic1</i> promoter methylation combined with the CEA level (parallel testing)</p><p>Sensitivity and specificity of markers detected in the gastric cancer (GC) group.</p

Representative <i>Zic1</i> promoter methylation, as determined by methylation-specific polymerase chain reaction (MSP) assay.

<p>M: Methylation-specific primers; U: Unmethylated-specific primers.</p

Sensitivity and specificity of markers detected in the gastric intraepithelial neoplasia (GPI) group.

<p>*: <i>Zic1</i> promoter methylation combined with the CEA level (tandem testing)</p><p>/: <i>Zic1</i> promoter methylation combined with the CEA level (parallel testing)</p><p>Sensitivity and specificity of markers detected in the gastric intraepithelial neoplasia (GPI) group.</p

Combined detection of <i>Zic1</i> promoter methylation and the CEA level (parallel testing) in gastric cancer (GC) plasma specimens.

<p>An ROC curve for evaluating the significance of the combined detection of the two parameters for GC diagnosis.</p