Sungwhan An - Academia.edu (original) (raw)

Papers by Sungwhan An

Research paper thumbnail of Comparative detection of syndecan-2 (SDC2) methylation in preoperative and postoperative stool DNA in patients with colorectal cancer

Background: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morb... more Background: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis, and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results. This study aimed to determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC. Methods: In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment...

Research paper thumbnail of Genetic and Epigenetic Marker-Based DNA Test of Stool Is a Promising Approach for Colorectal Cancer Screening

Yonsei Medical Journal, 2009

Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-relate... more Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-related deaths in the world. 1 However, it may be treated effectively by surgical removal of the cancerous tissue if detected at early stages. Conventional tools for screening CRC are either invasive or inaccurate. Therefore, there is an urgent need to develop a reliable screening tools for CRC to significantly reduce its morbidity. In this regard, a novel DNA markers-based detection in stool is emerging as a promising approach.

Research paper thumbnail of Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA

Research paper thumbnail of 428: Stool Dna-Based SYNDECAN-2(SDC2) Methylation Testing for the Early Detection of Colorectal Cancer in an Average Risk Population

Research paper thumbnail of Diagnostic Model for the Detection of BRAFV600EMutation by Using Receiver Operating Characteristic Curve of Pyrosequencing Analysis in Fine Needle Aspiration Biopsy Samples of Thyroid Nodules

Research paper thumbnail of Taejeong Oh

Multiple cytosine guanine dinucleotides (CpG island) are found in the VIM promoter region. The le... more Multiple cytosine guanine dinucleotides (CpG island) are found in the VIM promoter region. The levels of VIM pro-moter methylation and VIM gene expression were investi-gated in 7 cervical cancer cell lines and 50 human tissue samples with a distinctive degree of malignant trans-for-mation. While multiple CpG sites in the VIM promoter were highly methylated in CIN III and invasive carcinoma cells, they were rarely methylated in normal cells. Our result shows that methylation in the VIM promoter appears to start from CIN I and CIN II, relatively early stages of multi-step carcinogenesis. This epigenetic alteration in VIM promoter suggests the availability as a biomarker for the early diagnosis and prevention of cervical cancer. We also show that hypermethylation in the VIM promoter is re-sponsible for transcriptional silencing of the VIM gene in cervical cancer cells. In addition, our result shows that exogenous overexpression of the VIM gene in SiHa cer-vical cancer cells slightly ac...

Research paper thumbnail of MP16-15 CLINICAL Validation of Urine Dna-Based Penk Methylation Test for Detecting Bladder Cancer in Hematuria Patients

Research paper thumbnail of Systematic discovery of novel methylation biomarkers in colon cancer

Cancer Epidemiology and Prevention Biomarkers, 2006

B22 The aberrant methylation of CpG islands on promoter region of genes is common epigenetic phen... more B22 The aberrant methylation of CpG islands on promoter region of genes is common epigenetic phenomenon found early in cancers. This alteration contributes to cancer formation through the gene silencing of associated tumor suppressor genes. The aim of this study were to develop a systematic and stepwise genome-wide screening system for discovery of a new panel of genes enables to represent the high frequency of promoter hypermethylation in the development of colon cancer. We firstly determined a subset of genes relatively decreased in gene expression in colon cancers compared with their normal appearing-adjacent parts from 5 patients using human 17K cDNA microarray. We secondly analyzed expression profiles to identify genes epigenetically reactivated in two colon cancer cell lines after treatment with methylating inhibiting agent, 5 aza-29-deoxycytidine. We obtained 45 genes by cross-comparison of two gene lists and eliminated 18 genes not having CpG islands. We then carried out exa...

Research paper thumbnail of Gene expression profile of human mammary epithelial cells in response to 2,3,7,8-tetrachrodibenzo-p-dioxin

Organohalogen compounds, 2002

Research paper thumbnail of Translation gene expression profiling into the identification of high frequency of methylation markers in cervical neoplasia: novel panel of 3 genes of the CpG island methylator phenotype(CIMP) for high-grade squamous intraepithelial (HSIL) or worse

Clinical Cancer Research, 2006

A101 We have developed a systematic and stepwise genome-scale screening system to discover a new ... more A101 We have developed a systematic and stepwise genome-scale screening system to discover a new panel of genes enable to represent the high frequency of promoter methylation in the cervical cancer and its precursor lesions including carcinoma in situ (CIS) and high-grade squamous intraepithelial(HSIL). Considering that aberrant promoter methylation-mediated silencing of tumor suppressor genes has significant tissue specificity, we firstly investigated a subset of genes relatively decreased in gene expression in cervical cancer(CC) and biopsy specimens of precursor lesions (CC in 8, CIS in 2, and HSIL in 5) compared with normal-appearing biopsies in 7 using 35K microarray. We secondly analyzed expression profiles to identify genes epigenetically reactivated in four CC derived cell lines after treatment with methylation inhibiting agent, 5-aza-29-deoxycytidine. We obtained 53 genes by cross-comparison two gene lists and reduced to 28 through two additional steps, in silico search for...

Research paper thumbnail of Coronavirus Transcription Early in Infection

Journal of Virology, 1998

We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus (MHV) RNAs early... more We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus (MHV) RNAs early in infection by using cloned MHV defective interfering (DI) RNA that contained an intergenic sequence from which subgenomic DI RNA is synthesized in MHV-infected cells. Genomic DI RNA and subgenomic DI RNA accumulated at a constant ratio from 3 to 11 h postinfection (p.i.) in the cells infected with MHV-containing DI particles. Earlier, at 1 h p.i., this ratio was not constant; only genomic DI RNA accumulated, indicating that MHV RNA replication, but not MHV RNA transcription, was active during the first hour of MHV infection. Negative-strand genomic DI RNA and negative-strand subgenomic DI RNA were first detectable at 1 and 3 h p.i., respectively, and the amounts of both RNAs increased gradually until 6 h p.i. These data showed that at 2 h p.i., subgenomic DI RNA was undergoing synthesis in the cells in which negative-strand subgenomic DI RNA was undetectable. These data, therefore, si...

Research paper thumbnail of Colon Cancer Biomarker Discovery

Research paper thumbnail of Asthma-Predictive Genetic Markers in Gene Expression Profiling of Peripheral Blood Mononuclear Cells

an important issue because such genes may promote the early detection, positive prognosis, and tr... more an important issue because such genes may promote the early detection, positive prognosis, and treatment of the disease. To this end, large-scale, high-throughput, whole-genome studies are needed to understand the genomic contribution to asthma. Although many approaches have been used to investigate relationships between diseases and genes, the high-throughput microarray is one of the most important. Microarray technology allows the monitoring of gene expression on a genomic scale. It

Research paper thumbnail of The role of ADCYAP1, adenylate cyclase activating polypeptide 1, as a methylation biomarker for the early detection of cervical cancer

Oncology Reports, 2010

The ADCYAP1 gene encodes an adenylate cyclase activating polypeptide 1. ADCYAP1 has been known to... more The ADCYAP1 gene encodes an adenylate cyclase activating polypeptide 1. ADCYAP1 has been known to be involved in various biological processes. Multiple cytosine guanine dinucleotides (CpG island) are found in the ADCYAP1 promoter region. Transcriptional silencing by promoter hypermethylation is an important regulatory mechanism in tumorigenesis in many cancers. Therefore, the methylation level of the ADCYAP1 promoter was investigated in eight cervical cancer cell lines and human tissue samples with a distinctive degree of malignant transformation. While multiple CpG sites in the ADCYAP1 promoter were highly methylated in CIN III and invasive carcinoma cells as well as seven cervical cancer cell lines, they were rarely methylated in normal cells. Importantly, methylation in the ADCYAP1 promoter seems to start from CIN I, relatively early stage of multistep carcinogenesis. This fact suggest that ADCYAP1 can be used as an effective and sensitive methylation biomarker for the early diagnosis of cervical cancer. Moreover, our data imply that the level of the ADCYAP1 promoter hypermethylation is correlated with cervical cancer development. We also show that ADCYAP1 gene expression was reactivated by the treatment of a DNA methyltransferase inhibitor of 5'-aza-2'deoxycytidine and/or a histone deacetylase inhibitor of trichostain A in cervical cancer cells suggesting that hypermethylation in the ADCYAP1 promoter is responsible for the transcriptional silencing of the ADCYAP1 gene in cervical cancer cells.

Research paper thumbnail of Gene Expression Pattern in Caco-2 Cells following Rotavirus Infection

Journal of Virology, 2002

Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and you... more Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and young children worldwide. Preventive and therapeutic strategies are urgently needed to fight this pathogen. In tissue culture and in vivo, rotavirus induces structural and functional alterations in the host cell. In order to better understand the molecular mechanisms involved in the events after rotavirus infection, we identified host cellular genes whose mRNA levels changed after infection. For this analysis, we used microarrays containing more than 38,000 human cDNAs to study the transcriptional response of the human intestinal cell line Caco-2 to rotavirus infection. We found that 508 genes were differentially regulated >2-fold at 16 h after rotavirus infection, and only one gene was similarly regulated at 1 h postinfection. Of these transcriptional changes, 73% corresponded to the upregulation of genes, with the majority of them occurring late, at 12 or more hours postinfection. Some...

Research paper thumbnail of Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

Journal of Molecular Endocrinology, 2005

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabe... more Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats a...

Research paper thumbnail of Detection of HOXA9 gene methylation in tumor tissues and induced sputum samples from primary lung cancer patients

Clinical Chemistry and Laboratory Medicine, 2011

Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening moda... more Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening modality exists for lung cancer. We aimed to evaluate the prevalence of HOXA9 promoter methylation in tissue and induced sputum samples from Korean patients with lung cancer. Using pyrosequencing, HOXA9 methylation was analyzed for 40 pairs of primary lung cancer and normal tissues and 185 induced sputum specimens, including 76 patients with lung cancer. The methylation of HOXA9 in lung cancer tissue was significantly higher compared with normal tissues (67.4% ± 17.6% vs. 23.6% ± 10.3%, respectively; p<0.001). With a cut-off of >45.6% of HOXA9 gene methylation in tissues, the sensitivity was 90.5% and the specificity was 97.5%. In induced sputum specimens, the HOXA9 gene in lung cancer patients was significantly more hypermethylated compared with patients with benign lung diseases and the healthy group (23.4% ± 15.9%, 14.9% ± 7.9%, and 9.7% ± 5.0%, respectively; p<0.001). The HOXA9 gene was hypermethylated in 32 of 40 tumors (80%), especially in early stages of lung cancer. HOXA9 methylation could be a potential biomarker to aid early detection and prognosis.

Research paper thumbnail of Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Oncology Reports, 2012

Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA meth... more Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cutoff values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, P<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genomewide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.

Research paper thumbnail of Epigenetic regulation of the potential tumor suppressor gene, hLHX6.1, in human cervical cancer

It is well known that the Homo sapiens LIM homeobox domain 6 gene (hLHX6), a putative transcripti... more It is well known that the Homo sapiens LIM homeobox domain 6 gene (hLHX6), a putative transcription regulator, controls the differentiation and development of neural and lymphoid cells, particularly in the central nervous system. In this study, we investigated hLHX6.1 (an isoform of hLHX6), which functions as a tumor suppressor gene in the cervix. Firstly, the methylation levels of the hLHX6 and hLHX6.1 promoters were investigated in 8 cervical cancer cell lines and human tissue samples with a distinctive degree of malignant transformation. In spite of the presence of multiple cytosine guanine dinucleotides (CpG islands) in 2 proximal promoters of the hLHX6 and hLHX6.1 genes, only the hLHX6.1 promoters were found to be mostly hypermethylated and associated with transcriptional silencing by promoter methylation, whereas the hLHX6 promoters were not. Methylation levels in the hLHX6.1 promoter were also found to be strongly related to cervical cancer development. The level of hLHX6.1 gene expression was found to be relatively high in normal cells, in which the hLHX6.1 promoter was mostly unmethylated. However, the hLHX6.1 gene expression was down-regulated or undetectable in cervical cancer cell lines and cancer tissues, in which the hLHX6.1 promoter was hypermethylated. This epigenetic alteration in the hLHX6.1 promoter begins at a relatively early stage, suggesting its potential as a biomarker for the early diagnosis and prevention of cervical cancer. Moreover, the overexpression of the hLHX6.1 gene in cervical cancer cells suppressed the tumorigenic phenotype, as shown by soft agar colony formation and migration assays, suggesting that hLHX6.1 could be a new tumor suppressor gene in the cervix.

Research paper thumbnail of Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

BMC Gastroenterology

Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with m... more Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central lab...

Research paper thumbnail of Comparative detection of syndecan-2 (SDC2) methylation in preoperative and postoperative stool DNA in patients with colorectal cancer

Background: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morb... more Background: Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis, and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results. This study aimed to determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC. Methods: In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment...

Research paper thumbnail of Genetic and Epigenetic Marker-Based DNA Test of Stool Is a Promising Approach for Colorectal Cancer Screening

Yonsei Medical Journal, 2009

Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-relate... more Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-related deaths in the world. 1 However, it may be treated effectively by surgical removal of the cancerous tissue if detected at early stages. Conventional tools for screening CRC are either invasive or inaccurate. Therefore, there is an urgent need to develop a reliable screening tools for CRC to significantly reduce its morbidity. In this regard, a novel DNA markers-based detection in stool is emerging as a promising approach.

Research paper thumbnail of Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA

Research paper thumbnail of 428: Stool Dna-Based SYNDECAN-2(SDC2) Methylation Testing for the Early Detection of Colorectal Cancer in an Average Risk Population

Research paper thumbnail of Diagnostic Model for the Detection of BRAFV600EMutation by Using Receiver Operating Characteristic Curve of Pyrosequencing Analysis in Fine Needle Aspiration Biopsy Samples of Thyroid Nodules

Research paper thumbnail of Taejeong Oh

Multiple cytosine guanine dinucleotides (CpG island) are found in the VIM promoter region. The le... more Multiple cytosine guanine dinucleotides (CpG island) are found in the VIM promoter region. The levels of VIM pro-moter methylation and VIM gene expression were investi-gated in 7 cervical cancer cell lines and 50 human tissue samples with a distinctive degree of malignant trans-for-mation. While multiple CpG sites in the VIM promoter were highly methylated in CIN III and invasive carcinoma cells, they were rarely methylated in normal cells. Our result shows that methylation in the VIM promoter appears to start from CIN I and CIN II, relatively early stages of multi-step carcinogenesis. This epigenetic alteration in VIM promoter suggests the availability as a biomarker for the early diagnosis and prevention of cervical cancer. We also show that hypermethylation in the VIM promoter is re-sponsible for transcriptional silencing of the VIM gene in cervical cancer cells. In addition, our result shows that exogenous overexpression of the VIM gene in SiHa cer-vical cancer cells slightly ac...

Research paper thumbnail of MP16-15 CLINICAL Validation of Urine Dna-Based Penk Methylation Test for Detecting Bladder Cancer in Hematuria Patients

Research paper thumbnail of Systematic discovery of novel methylation biomarkers in colon cancer

Cancer Epidemiology and Prevention Biomarkers, 2006

B22 The aberrant methylation of CpG islands on promoter region of genes is common epigenetic phen... more B22 The aberrant methylation of CpG islands on promoter region of genes is common epigenetic phenomenon found early in cancers. This alteration contributes to cancer formation through the gene silencing of associated tumor suppressor genes. The aim of this study were to develop a systematic and stepwise genome-wide screening system for discovery of a new panel of genes enables to represent the high frequency of promoter hypermethylation in the development of colon cancer. We firstly determined a subset of genes relatively decreased in gene expression in colon cancers compared with their normal appearing-adjacent parts from 5 patients using human 17K cDNA microarray. We secondly analyzed expression profiles to identify genes epigenetically reactivated in two colon cancer cell lines after treatment with methylating inhibiting agent, 5 aza-29-deoxycytidine. We obtained 45 genes by cross-comparison of two gene lists and eliminated 18 genes not having CpG islands. We then carried out exa...

Research paper thumbnail of Gene expression profile of human mammary epithelial cells in response to 2,3,7,8-tetrachrodibenzo-p-dioxin

Organohalogen compounds, 2002

Research paper thumbnail of Translation gene expression profiling into the identification of high frequency of methylation markers in cervical neoplasia: novel panel of 3 genes of the CpG island methylator phenotype(CIMP) for high-grade squamous intraepithelial (HSIL) or worse

Clinical Cancer Research, 2006

A101 We have developed a systematic and stepwise genome-scale screening system to discover a new ... more A101 We have developed a systematic and stepwise genome-scale screening system to discover a new panel of genes enable to represent the high frequency of promoter methylation in the cervical cancer and its precursor lesions including carcinoma in situ (CIS) and high-grade squamous intraepithelial(HSIL). Considering that aberrant promoter methylation-mediated silencing of tumor suppressor genes has significant tissue specificity, we firstly investigated a subset of genes relatively decreased in gene expression in cervical cancer(CC) and biopsy specimens of precursor lesions (CC in 8, CIS in 2, and HSIL in 5) compared with normal-appearing biopsies in 7 using 35K microarray. We secondly analyzed expression profiles to identify genes epigenetically reactivated in four CC derived cell lines after treatment with methylation inhibiting agent, 5-aza-29-deoxycytidine. We obtained 53 genes by cross-comparison two gene lists and reduced to 28 through two additional steps, in silico search for...

Research paper thumbnail of Coronavirus Transcription Early in Infection

Journal of Virology, 1998

We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus (MHV) RNAs early... more We studied the accumulation kinetics of murine coronavirus mouse hepatitis virus (MHV) RNAs early in infection by using cloned MHV defective interfering (DI) RNA that contained an intergenic sequence from which subgenomic DI RNA is synthesized in MHV-infected cells. Genomic DI RNA and subgenomic DI RNA accumulated at a constant ratio from 3 to 11 h postinfection (p.i.) in the cells infected with MHV-containing DI particles. Earlier, at 1 h p.i., this ratio was not constant; only genomic DI RNA accumulated, indicating that MHV RNA replication, but not MHV RNA transcription, was active during the first hour of MHV infection. Negative-strand genomic DI RNA and negative-strand subgenomic DI RNA were first detectable at 1 and 3 h p.i., respectively, and the amounts of both RNAs increased gradually until 6 h p.i. These data showed that at 2 h p.i., subgenomic DI RNA was undergoing synthesis in the cells in which negative-strand subgenomic DI RNA was undetectable. These data, therefore, si...

Research paper thumbnail of Colon Cancer Biomarker Discovery

Research paper thumbnail of Asthma-Predictive Genetic Markers in Gene Expression Profiling of Peripheral Blood Mononuclear Cells

an important issue because such genes may promote the early detection, positive prognosis, and tr... more an important issue because such genes may promote the early detection, positive prognosis, and treatment of the disease. To this end, large-scale, high-throughput, whole-genome studies are needed to understand the genomic contribution to asthma. Although many approaches have been used to investigate relationships between diseases and genes, the high-throughput microarray is one of the most important. Microarray technology allows the monitoring of gene expression on a genomic scale. It

Research paper thumbnail of The role of ADCYAP1, adenylate cyclase activating polypeptide 1, as a methylation biomarker for the early detection of cervical cancer

Oncology Reports, 2010

The ADCYAP1 gene encodes an adenylate cyclase activating polypeptide 1. ADCYAP1 has been known to... more The ADCYAP1 gene encodes an adenylate cyclase activating polypeptide 1. ADCYAP1 has been known to be involved in various biological processes. Multiple cytosine guanine dinucleotides (CpG island) are found in the ADCYAP1 promoter region. Transcriptional silencing by promoter hypermethylation is an important regulatory mechanism in tumorigenesis in many cancers. Therefore, the methylation level of the ADCYAP1 promoter was investigated in eight cervical cancer cell lines and human tissue samples with a distinctive degree of malignant transformation. While multiple CpG sites in the ADCYAP1 promoter were highly methylated in CIN III and invasive carcinoma cells as well as seven cervical cancer cell lines, they were rarely methylated in normal cells. Importantly, methylation in the ADCYAP1 promoter seems to start from CIN I, relatively early stage of multistep carcinogenesis. This fact suggest that ADCYAP1 can be used as an effective and sensitive methylation biomarker for the early diagnosis of cervical cancer. Moreover, our data imply that the level of the ADCYAP1 promoter hypermethylation is correlated with cervical cancer development. We also show that ADCYAP1 gene expression was reactivated by the treatment of a DNA methyltransferase inhibitor of 5'-aza-2'deoxycytidine and/or a histone deacetylase inhibitor of trichostain A in cervical cancer cells suggesting that hypermethylation in the ADCYAP1 promoter is responsible for the transcriptional silencing of the ADCYAP1 gene in cervical cancer cells.

Research paper thumbnail of Gene Expression Pattern in Caco-2 Cells following Rotavirus Infection

Journal of Virology, 2002

Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and you... more Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and young children worldwide. Preventive and therapeutic strategies are urgently needed to fight this pathogen. In tissue culture and in vivo, rotavirus induces structural and functional alterations in the host cell. In order to better understand the molecular mechanisms involved in the events after rotavirus infection, we identified host cellular genes whose mRNA levels changed after infection. For this analysis, we used microarrays containing more than 38,000 human cDNAs to study the transcriptional response of the human intestinal cell line Caco-2 to rotavirus infection. We found that 508 genes were differentially regulated >2-fold at 16 h after rotavirus infection, and only one gene was similarly regulated at 1 h postinfection. Of these transcriptional changes, 73% corresponded to the upregulation of genes, with the majority of them occurring late, at 12 or more hours postinfection. Some...

Research paper thumbnail of Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

Journal of Molecular Endocrinology, 2005

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabe... more Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats a...

Research paper thumbnail of Detection of HOXA9 gene methylation in tumor tissues and induced sputum samples from primary lung cancer patients

Clinical Chemistry and Laboratory Medicine, 2011

Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening moda... more Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening modality exists for lung cancer. We aimed to evaluate the prevalence of HOXA9 promoter methylation in tissue and induced sputum samples from Korean patients with lung cancer. Using pyrosequencing, HOXA9 methylation was analyzed for 40 pairs of primary lung cancer and normal tissues and 185 induced sputum specimens, including 76 patients with lung cancer. The methylation of HOXA9 in lung cancer tissue was significantly higher compared with normal tissues (67.4% ± 17.6% vs. 23.6% ± 10.3%, respectively; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). With a cut-off of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;45.6% of HOXA9 gene methylation in tissues, the sensitivity was 90.5% and the specificity was 97.5%. In induced sputum specimens, the HOXA9 gene in lung cancer patients was significantly more hypermethylated compared with patients with benign lung diseases and the healthy group (23.4% ± 15.9%, 14.9% ± 7.9%, and 9.7% ± 5.0%, respectively; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The HOXA9 gene was hypermethylated in 32 of 40 tumors (80%), especially in early stages of lung cancer. HOXA9 methylation could be a potential biomarker to aid early detection and prognosis.

Research paper thumbnail of Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Oncology Reports, 2012

Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA meth... more Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cutoff values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, P<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genomewide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.

Research paper thumbnail of Epigenetic regulation of the potential tumor suppressor gene, hLHX6.1, in human cervical cancer

It is well known that the Homo sapiens LIM homeobox domain 6 gene (hLHX6), a putative transcripti... more It is well known that the Homo sapiens LIM homeobox domain 6 gene (hLHX6), a putative transcription regulator, controls the differentiation and development of neural and lymphoid cells, particularly in the central nervous system. In this study, we investigated hLHX6.1 (an isoform of hLHX6), which functions as a tumor suppressor gene in the cervix. Firstly, the methylation levels of the hLHX6 and hLHX6.1 promoters were investigated in 8 cervical cancer cell lines and human tissue samples with a distinctive degree of malignant transformation. In spite of the presence of multiple cytosine guanine dinucleotides (CpG islands) in 2 proximal promoters of the hLHX6 and hLHX6.1 genes, only the hLHX6.1 promoters were found to be mostly hypermethylated and associated with transcriptional silencing by promoter methylation, whereas the hLHX6 promoters were not. Methylation levels in the hLHX6.1 promoter were also found to be strongly related to cervical cancer development. The level of hLHX6.1 gene expression was found to be relatively high in normal cells, in which the hLHX6.1 promoter was mostly unmethylated. However, the hLHX6.1 gene expression was down-regulated or undetectable in cervical cancer cell lines and cancer tissues, in which the hLHX6.1 promoter was hypermethylated. This epigenetic alteration in the hLHX6.1 promoter begins at a relatively early stage, suggesting its potential as a biomarker for the early diagnosis and prevention of cervical cancer. Moreover, the overexpression of the hLHX6.1 gene in cervical cancer cells suppressed the tumorigenic phenotype, as shown by soft agar colony formation and migration assays, suggesting that hLHX6.1 could be a new tumor suppressor gene in the cervix.

Research paper thumbnail of Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

BMC Gastroenterology

Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with m... more Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central lab...