Epigenetic inactivation of RUNX3 in colorectal cancer.

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

The Relationship between RUNX3 Inactivation and Its Pathological Features in Renal Cell Carcinoma

PURPOSE: DNA methylation is a key regulator of gene transcription and genomic stability, and alterations in DNA methylation are frequently detected in human tumors. Recent study has suggested that inactivation of runt-related transcription factor 3 (RUNX3), primarily epigenetic alterations in DNA methylation, is closely associated with bladder tumor stage, grade, and prognosis. The aim of this study was to evaluate the association between RUNX3 inactivation and renal cell carcinoma (RCC). MATERIALS AND METHODS: RCC tissues (n=56) were obtained from patients who underwent radical nephrectomy. The methylation pattern of RUNX3 was determined by using methylation specific-polymerase chain reaction (MS-PCR) and direct DNA sequencing. RESULTS: Methylation of the RUNX3 promoter was observed in 75.0% of the samples (42/56). The tumor stage and grade were significantly associated with the methylation status (p0.05, respectively). CONCLUSIONS: This study demonstrated that promoter methylation of RUNX3 is frequently observed in RCC. In addition, RUNX3 methylation is closely associated with aggressive pathologic features.

Expression of Runx3 protein and its cliniopathologic significance in gastric carcinoma / 临床与实验病理学杂志

Purpose To investigate the relationship between the expression of Runx3 protein and pathogenesis, development,clinicopathological features and its prognostic significance in gastric adenocarcinoma.Methods Immunohistochemical SP method was used to detect the expression of Runx3 protein in 63 cases of gastric cancer,19 cases of atypical hyperplasia and 10 cases of normal gastric mucosa obtained from patients whose partial gastrotomy was performed for benign diseases.Results Compared with gastric atypical hyperplasia tissue (68.4%) and normal gastric mucosa (90%), the positive rate of Runx3 protein in gastric cancer (39.7%) was significantly lower (P＜0.05); the expression of Runx3 protein was related to tumor differentiation, invasive depth and lymphnode metastasis, but not to age, sex, tumor size and TNM stages; the survival rate of the patients with Runx3 protein expression was higher than that without Runx3 expression (P＜0.05).Conclusion Runx3 protein may play an important role in the occurrence and development of gastric cancer, and it is an important marker in evaluating the prognosis of the patients.

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma.

BACKGROUND/AIMS: RUNX3 (PEBP2alphaC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. METHODS: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. RESULTS: Comparison of the results with the clinicopathological characteristics identified RUNX3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well- and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren's classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). CONCLUSIONS: Methylation of the tumor suppressor gene RUNX3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma.

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma

BACKGROUND/AIMS: RUNX3 (PEBP2alphaC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. METHODS: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. RESULTS: Comparison of the results with the clinicopathological characteristics identified RUNX3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well- and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren's classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). CONCLUSIONS: Methylation of the tumor suppressor gene RUNX3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma.

The Causal Relationship between RUNX3 and Bladder Tumor / 대한비뇨기과학회지

PURPOSE: We investigated the methylation pattern of RUNX3 to determine whether aberrant methylation events are risk factors for bladder tumor development, recurrence, and progression. MATERIALS AND METHODS: A hospital based, case-control investigation was carried out in 124 bladder tumor specimens and 20 normal bladder mucosae. The methylation pattern of RUNX3 was determined using MS- PCR and direct DNA sequencing. RUNX3 mRNA expression levels were assessed by RT-PCR. RESULTS: All normal bladder mucosae were unmethylated. On the other hand, bladder tumor tissues showed either unmethylated, methylated, or both unmethylated and methylated patterns. Methylation of RUNX3 promoter region was significant as a risk factor for bladder tumor development (p<0.01, OR=107.55, 95% CI=6.33-1827.39). The methylation type was more frequent in invasive tumors, compared with superficial bladder tumors (p=0.01, OR=2.95, 95% CI=1.16-7.47). Both recurrence (p=0.02, OR= 3.70, 95% CI=1.19-11.46) and subsequent tumor progression were significantly associated with the methylation of the RUNX3 promoter region (p=0.01, OR=5.63, 95% CI=1.23-25.82). The mutations in 3 cases out of 23 bladder tumor tissues were observed in contrast with normal bladder mucosae. CONCLUSIONS: These results suggest not only the possibility that RUNX3 is a tumor suppressor gene responsible for bladder tumor, but also that it may be a useful prognostic marker for bladder tumor recurrence and progression.