Methylation of the HACE1 gene is frequently detected in hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas. METHODOLOGY: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP). RESULTS: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC. The clinicopathological data were then correlated with these results. In the value of serum AFP (α-fetoprotein), a significant difference was observed (p=0.0025). CONCLUSIONS: All stages of HCCs presented HACE1 methylation, indicating that the HACE1 gene has been methylated from the early stages of HCCs.

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS: WNT5A was more frequently methylated in early gastric carcinomas.

Methylation of the DFNA5 gene is frequently detected in colorectal cancer.

BACKGROUND: Recently, the human deafness, autosomal dominant 5 gene, DFNA5, has frequently been detected in cancer tissues. The methylation status of the DFNA5 gene in colorectal cancer was examined and was compared to the clinocopathological findings. MATERIALS AND METHODS: Eighty-five tumor samples and corresponding normal tissues were obtained from patients with colorectal cancer who underwent surgery at our hospital. The methylation status of the DFNA5 gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the DFNA5 gene. RESULTS: DFNA5 gene methylation was found in 29 (34%) out of the 85 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant correlation with methylation was observed for lymphatic vessel invasion and TNM stage (p=0.0268 and p=0.0189, respectively). CONCLUSION: DFNA5 might act as a tumor suppressor gene and DFNA5 gene methylation might play an important role in the development of colorectal cancer. Our data implicate DFNA5 gene methylation as a novel molecular biomarker in colorectal cancer.

Methylation of the homeobox gene, HOPX, is frequently detected in poorly differentiated colorectal cancer.

BACKGROUND: Homeodomein only protein x (HOPX) gene methylation has frequently been detected in cancer tissues. The methylation status of the HOPX gene in colorectal cancer was examined and compared to the clinocopathological findings. MATERIALS AND METHODS: Eighty-nine tumor samples and corresponding normal tissues were obtained from colorectal cancer patients who underwent surgery at our hospital. The methylation status of the HOPX gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the HOPX gene. RESULTS: HOPX gene methylation was found in 46 (52%) out of the 89 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant increase of methylation was observed in the poorly differentiated carcinomas (p=0.0049). CONCLUSION: HOPX gene methylation could play an important role for the development of colorectal cancer and is closely related to the histological type.

MACC 1 as a marker for peritoneal-disseminated gastric carcinoma.

BACKGROUND: Recently, metastasis associated with the colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, the MACC1 expression levels were examined in colorectal carcinomas and it was found that MACC1 expression showed significant correlation with peritoneal dissemination and higher stage of TNM classification. MATERIALS AND METHODS: In this study, MACC1 expression levels were analysed in 41 gastric cancer samples using quantitative real-time polymerase chain reaction (QRT-PCR). Results. Distribution of MACC1 expression scores in primary gastric carcinomas was between 0.01 and 4.36 (average ± SD was 1.34 ± 1.31). Subsequently, clinicopathological data were correlated with the MACC1 expression. It was found that MACC1 expression showed significant correlation with peritoneal dissemination (p=0.038). CONCLUSION: These results suggest that MACC1 is more frequently expressed in peritoneal-disseminated gastric carcinomas and may serve as a new parameter for the prognostic prediction of gastric cancer.

[The usefulness and adverse events of bevacizumab combined with chemotherapy against advanced or recurrent colorectal cancer].

We examined clinical results of 35 patients on bevacizumab(BV)combined with chemotherapy at our hospital. The subjects were 35 patients with advanced or recurrent colorectal cancer who received BV combined with chemotherapy for approximately 2 years. Their median age was 66 years(41 to 86 years), PS was 2 or less for all; it was first-line therapy in 21 patients, second-line in 12 patients and thirdline in 2 patients. The concomitant chemotherapy was mFOLFOX 6 in 24 / patients, 5-FU/LV in 8 patients and FOLFIRI in 3 patients. Therapeutic efficacy was CR in 2 patients, PR in 10 patients, and the overall response rate was 35%. There were 7 adverse events of Grade 3 or higher, among which 4 events were leucopenia. Neither overall survival nor any concomitant chemotherapy reached the median periods. Moreover, the median periods of / progression-free survival in mFOLFOX6/FOLFIRI were 191 days. BV combined with chemotherapy should be actively introduced as first-line therapy against advanced or recurrent colorectal cancer because of its high therapeutic efficacy.

Demethylation of the CD133 gene is frequently detected in early gastric carcinoma.

BACKGROUND: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal and gastric carcinogenesis. MATERIALS AND METHODS: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Demethylation of the CD133 gene was detected in 14 out of the 36 (39%) primary gastric carcinomas, suggesting that the demethylation of CD133 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the demethylation results. A significant decrease of CD133 methylation was observed in the extent of tumor (p=0.0421). Moreover, a trend was shown toward smaller maximal tumor size in tumors with demethylated CD133 (p=0.0556). CONCLUSION: CD133 appears to be frequently demethylated in early gastric carcinomas.

Methylation of the DCC gene is lost in advanced gastric cancer.

BACKGROUND: Deleted in colorectal carcinoma (DCC), one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, we examined the methylation status of the DCC gene in colorectal carcinomas and found that aberrant methylation of the DCC gene was detected in 28 out of the 50 (56%) primary colon carcinomas. This result prompted us to examine the methylation status of the DCC gene in gastric carcinoma. MATERIALS AND METHODS: The methylation status of the DCC gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the DCC gene was detected in 16 out of the 36 (44%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0093). CONCLUSION: DCC methylation was observed in the course of gastric carcinogenesis and disappeared in advanced gastric carcinoma.

PGP9.5 was less frequently methylated in advanced gastric carcinoma.

BACKGROUND/AIMS: Recently, it was examined the methylation status of the Protein Gene Product 9.5 (PGP9.5) gene in primary tumors derived from 49 patients with colorectal cancer and evaluated the correlation between the methylation status and the clinicopathological findings. A significant difference was observed in lymph node metastasis (p = 0.029), suggesting that PGP9.5 was less frequently methylated in metastatic colorectal cancer. This result prompted us to examine the methylation status of the PGP9.5 gene in gastric cancers. METHODOLOGY: It was examined the methylation status of the PGP9.5 gene in primary tumors derived from 30 patients with gastric cancer using qMSP and evaluated the correlation between the methylation status and the clinicopathological findings. RESULTS: Aberrant methylation of the PGP9.5 gene was detected in 5 of 30 (17%) primary gastric cancers. The present results suggested that the aberrant methylation of the PGP9.5 gene was frequently observed in gastric cancers. Subsequently, clinicopathological data were correlated with the methylation results. A significant difference was observed in extent of tumor, lymph node metastasis, and TNM stage (p = 0.034, 0.015, and 0.028, respectively). CONCLUSION: PGP9.5 was less frequently methylated in advanced gastric cancer compared to earlier one.

Changes in UNC5C gene methylation during human gastric carcinogenesis.

BACKGROUND: UNC5C, one of the netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, aberrant methylation of the UNC5C gene was found in 34 out of 49 (69%) primary colon carcinomas. MATERIALS AND METHODS: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 36 patients with gastric cancer using quantitative methylation-specific polymerase chain reaction, and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the UNC5C gene was detected in 9 out of the 36 (25%) primary gastric carcinomas. A significant difference was observed in regard to the TNM stage (p=0.0455). CONCLUSION: UNC5C methylation was observed in the course of gastric carcinogenesis and disappeared in highly advanced gastric carcinomas.

Frequent CDH3 demethylation in advanced gastric carcinoma.

BACKGROUND: We recently found that CDH3 was frequently demethylated in advanced colorectal carcinomas. This prompted us to examine the demethylation status of the CDH3 gene in gastric carcinomas. MATERIALS AND METHODS: The demethylation status of the CDH3 gene was examined in primary tumors derived from 36 patients with gastric carcinoma using a quantitative methylation-specific PCR (qMSP) and was evaluated the correlation between the demethylation status and the clinicopathological findings. RESULTS: Demethylation of the CDH3 gene was detected in 25 out of the 36 (69%) primary gastric carcinomas, suggesting that the aberrant demethylation of CDH3 is a frequent event in gastric carcinomas. Demethylation of CDH3 was significantly associated with increasing TNM stage (p=0.0261). Moreover, a trend was shown toward infiltration beyond the serosa being associated with demethylation of CDH3 (p=0.0733). CONCLUSION: CDH3 was frequently demethylated in advanced gastric carcinomas.

Down-regulation of Tip60 gene as a potential marker for the malignancy of colorectal cancer.

BACKGROUND: Recently, it was shown that the loss of human Tip60 leads to an accumulation of double-strand DNA breaks and is linked to a growing number of cancer types. PATIENTS AND METHODS: Tip60 expression levels were in examined in 38 colorectal cancer samples using a quantitative real-time polymerase chain reaction. Subsequently, clinicopathological data were correlated with the Tip60 expression score. RESULTS: A down-regulation of the Tip60 gene was observed 5 out of 38 (13%) specimens of primary colorectal cancer. Tip60 down-regulation showed significant correlation with larger tumor size (p=0.0005), poorly differentiated type (p=0.0394), peritoneal dissemination (p=0.0053), distant metastasis (p=0.0394), and higher stage of TNM classification (p=0.0226). CONCLUSION: These results suggested that Tip60 was more frequently down-regulated in advanced colorectal carcinoma.

CD133 gene overexpression is frequently observed in early colorectal carcinoma.

BACKGROUND/AIMS: Recently, it has been proved that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells. The present study examined the CD133 gene expression in colorectal carcinomas we surgically removed. METHODOLOGY: The CD133 gene expression in primary tumors and corresponding normal tissues derived from 30 patients with colorectal carcinoma was examined using a quantitative reverse-transcription PCR (QRT-PCR) and evaluated the correlation between the CD133 gene expression levels and the clinicopathological findings. RESULTS: An increase in CD133 expression scores was observed in Dukes A's colorectal carcinomas (1.70 +/- 2.28) compared to Dukes B and C's colorectal carcinomas (0.76 +/- 0.71) (p = 0.0860). An increase in CD133 expression scores was also observed in female colorectal carcinomas (1.29 +/- 1.56) compared to male colorectal carcinomas (0.61 +/- 0.57) (p = 0.125). CONCLUSIONS: CD133 gene overexpression in early colorectal cancer patients was more frequently observed than in advanced cases.

WNT5A gene is aberrantly methylated from the early stages of colorectal cancers.

BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of these cancers remains unknown. METHODOLOGY: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the WNT5A gene was detected in 17 out of the 49 (35%) primary colorectal cancers. The clinicopathological data were correlated with the methylation results. All stages of colorectal cancers presented WNT5A methylation. CONCLUSIONS: WNT5A gene has been methylated from the early stages of colorectal cancers.

Demethylation of the CDH3 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been proven that the CDH3 promoter was hypomethylated in colonic aberrant foci and colorectal cancer. The hypomethylation was also associated with induction of CDH3 expression in colorectal cancer. These results indicated that epigenetic demethylation of the CDH3 promoter in the human intestine permits its ectopic expression in colorectal cancer. MATERIALS AND METHODS: The demethylation status of the CDH3 gene was examined in primary carcinomas and the corresponding normal tissues derived from 53 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the demethylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant demethylation of the CDH3 gene was detected in 41 out of the 53 (77%) primary colon carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the tumor site and Dukes' stage (p=0.0187 and p=0.0192, respectively). Moreover, a trend was shown toward preferentially developing tumor size (p=0.140). CONCLUSION: These results indicated that CDH3 was more frequently demethylated in advanced colorectal carcinomas.

Frequent methylation of Vimentin in well-differentiated gastric carcinoma.

BACKGROUND: Recently, it was shown that the vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma. MATERIALS AND METHODS: The methylation status of the vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 37 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the vimentin gene was detected in 14 out of 37 (38%) primary gastric carcinomas. This result suggested that the aberrant methylation of the vimentin gene was frequent in gastric carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in histology (p=0.0429). In addition, a trend was shown toward advancement of gastric carcinomas with vimentin methylation (p=0.0588). CONCLUSION: In gastric carcinomas, well-differentiated adenocarcinoma was significantly methylated compared to poorly differentiated.

Demethylation of the CD133 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal carcinogenesis. MATERIALS AND METHODS: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 48 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Demethylation of the CD133 gene was detected in 19 out of the 48 (40%) primary colon carcinomas, suggesting that the demethylation of CD133 is frequently observed in colorectal carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the maximal tumor size (p=0.0222). Moreover, a trend was shown toward preferentially developing lymph node metastasis in demethylated tumors (p=0.214). CONCLUSION: CD133 was more frequently demethylated in advanced colorectal carcinomas.

Methylation of HACE1 in gastric carcinoma.

BACKGROUND: We recently examined the methylation status of the HACE1 gene in primary carcinomas derived from 32 patients with colorectal cancer. A significant increase was observed in the maximal tumor size of the tumors with methylated HACE1 (p=0.0304). Moreover, a trend was shown toward preferentially developing lymph node metastasis in the carcinomas with methylated HACE1 (p=0.0612), suggesting that HACE1 might present a malignant potential in colorectal cancer. These results prompted us to examine the methylation status of the HACE1 gene in gastric carcinomas. MATERIALS AND METHODS: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 34 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: An aberrant methylation of the HACE1 gene was detected in 9 out of 34 (26%) primary gastric carcinomas. Subsequently, clinicopathological data were tested for correlation with the methylation score. A significant difference was observed in patient gender (p=0.0429). CONCLUSION: HACE1 was frequently methylated in gastric carcinoma derived from male patients.

Aberrant methylation of the UNC5C gene is frequently detected in advanced colorectal cancer.

BACKGROUND: UNC5C, one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, two reports indicated that UNC5C methylation was closely associated with loss of gene expression in colorectal cancer. MATERIALS AND METHODS: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with colorectal cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the UNC5C gene was detected in 34 out of the 49 (69%) primary colon carcinomas, suggesting that the aberrant methylation of UNC5C was frequent in colorectal cancer. The clinicopathological data were then tested for correlation with this result. A significantly greater proportion of cases with methylated UNC5C was found in Dukes' stage C (p = 0.0380) than in earlier stages. CONCLUSION: UNC5C might act as a tumor suppressor and UNC5C methylation might present a malignant potential in colorectal cancer.

Aberrant methylation of the p16 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: A tumor suppressor gene, p16, was found to harbor promoter hypermethylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation was important for colorectal tumorigenesis. MATERIALS AND METHODS: The methylation status of the p16 gene was examined in primary carcinomas and the corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the p16 gene was detected in 20 out of the 50 (40%) primary colon carcinomas, suggesting that the aberrant methylation of p16 was frequently observed in colorectal carcinomas. The clinicopathological data were then correlated with these results. Significant differences were observed with Dukes' stage (p = 0.0495) and lymphatic invasion (p = 0.0277). CONCLUSION: p16 might act as a tumor suppressor in colorectal carcinomas and was more frequently methylated in advanced colorectal carcinomas.