본문 바로가기
HOME> 저널/프로시딩 > 저널/프로시딩 검색상세

저널/프로시딩 상세정보

권호별목차 / 소장처보기

H : 소장처정보

T : 목차정보

Clinical epigenetics 130건

  1. [해외논문]   Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion   SCIE

    Bagacean, Cristina (U1227 B lymphocytes and autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, networks IC-CGO and REpiCGO from “Canceropole Grand Ouest”, Brest, France ) , Le Dantec, Christelle (U1227 B lymphocytes and autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, networks IC-CGO and REpiCGO from “Canceropole Grand Ouest”, Brest, France ) , Berthou, Christian (U1227 B lymphocytes and autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, networks IC-CGO and REpiCGO from “Canceropole Grand Ouest”, Brest, France ) , Tempescul, Adrian (U1227 B lymphocytes and autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, networks IC-CGO and REpiCGO from “Canceropole Grand Ouest”, Brest, France ) , Saad, Hussam (Department of Hematology, Brest University Medical School Hospital, Brest, France ) , Bordron, Anne (U1227 B lymphocytes and autoimmunity, University of Brest, INSERM, IBSAM, Labex IGO, networks IC-CGO and REpiCGO from “Canceropole Grand Ouest”, Brest, France ) , Zdrenghea, Mihnea (“Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania ) , Cristea, Victor (“Iuliu) , Douet-Guilbert, Nathalie , Renaudineau, Yves
    Clinical epigenetics v.9 no.1 ,pp. 122 , 2017 , 1868-7075 ,

    초록

    Background Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5-hydroxymethylcytosine (5-hmCyt), were tested by ELISA ( n = 60), while real-time quantitative PCR was used for determining transcriptional expression levels of DNMT and TET ( n = 24). Results By using global DNA methylation/demethylation levels, in the low-risk disease group, two subgroups with significantly different clinical outcomes have been identified (median treatment-free survival [TFS] 45 versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5-hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process. When considering the cytogenetic intermediate/high-risk disease groups, an association of 5-mCyt status with lymphocytosis ( p = 0.0008) and the lymphocyte doubling time ( p = 0.04) but not with TFS was observed, as well as a reduction of DNMT3A , TET1 , and TET2 transcripts. Conclusions Combining cytogenetic studies with 5-mCyt assessment adds accuracy to CLL patients' prognoses and particularly for those with 13q deletion as a sole cytogenetic abnormality.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  2. [해외논문]   Epigenetic modifications of the VGF gene in human non-small cell lung cancer tissues pave the way towards enhanced expression   SCIE

    Marwitz, Sebastian (Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck and the Research Center Borstel Parkallee 3, 23845 Borstel, Germany ) , Heinbockel, Lena (Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck and the Research Center Borstel Parkallee 3, 23845 Borstel, Germany ) , Scheufele, Swetlana (Institute of Human Genetics, University Medical Center Schleswig-Holstein (UKSH), D-24105 Kiel, Germany ) , Nitschkowski, Dö (Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck and the Research Center Borstel Parkallee 3, 23845 Borstel, Germany ) , rte (Surgery, LungenClinic Grosshansdorf, D-22927 Grosshansdorf, Germany ) , Kugler, Christian (Pathology of the University Medical Center Schleswig-Holstein (UKSH), Campus Lübeck and the Research Center Borstel Parkallee 3, 23845 Borstel, Germany ) , Perner, Sven (Oncology, LungenClinic Grosshansdorf, D-22927 Grosshansdorf, Germany ) , Reck, Martin (Institute of Human Genetics, University Medical Center Ulm, D-89081 Ulm, Germany ) , Ammerpohl, Ole (Pathology of the University Medica) , Goldmann, Torsten
    Clinical epigenetics v.9 no.1 ,pp. 123 , 2017 , 1868-7075 ,

    초록

    Hwang et al. recently showed that VGF substantially contributes to the resistance of human lung cancer cells towards epidermal growth factor receptor kinase inhibitors. This was further linked to enhanced epithelial–mesenchymal transition. Here, we demonstrate that VGF is epigenetically modified in non-small cell lung cancer tissues compared to corresponding tumor-free lung tissues from the same donors by using methylome bead chip analyses. These epigenetic modifications trigger an increased transcription of the VGF gene within the tumors, which then leads to an increased expression of the protein, facilitating epithelial–mesenchymal transition, and the resistance to kinase inhibitors. These results should be taken into account in the design of novel therapeutic and diagnostic approaches.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  3. [해외논문]   Novel insights into epigenetic drivers of oropharyngeal squamous cell carcinoma: role of HPV and lifestyle factors   SCIE

    Boscolo-Rizzo, Paolo (Department of Neurosciences, ENT Clinic and Regional Center for Head and Neck Cancer, Treviso Regional Hospital, University of Padova, Treviso, Italy ) , Furlan, Carlo (Division of Radiotherapy, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN Italy ) , Lupato, Valentina (Unit of Otolaryngology, General Hospital “S. Maria degli Angeli”, Pordenone, Italy ) , Polesel, Jerry (Unit of Cancer Epidemiology, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN Italy ) , Fratta, Elisabetta (Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN Italy)
    Clinical epigenetics v.9 no.1 ,pp. 124 , 2017 , 1868-7075 ,

    초록

    In the last years, the explosion of high throughput sequencing technologies has enabled epigenome-wide analyses, allowing a more comprehensive overview of the oropharyngeal squamous cell carcinoma (OPSCC) epigenetic landscape. In this setting, the cellular pathways contributing to the neoplastic phenotype, including cell cycle regulation, cell signaling, DNA repair, and apoptosis have been demonstrated to be potential targets of epigenetic alterations in OPSCC. Of note, it has becoming increasingly clear that HPV infection and OPSCC lifestyle risk factors differently drive the epigenetic machinery in cancer cells. Epigenetic changes, including DNA methylation, histone modifications, and non-coding RNA expression, can be used as powerful and reliable tools for early diagnosis of OPSCC patients and improve prognostication. Since epigenetic changes are dynamic and reversible, epigenetic enzymes may also represent suitable targets for the development of more effective OPSCC therapeutic strategies. Thus, this review will focus on the main known epigenetic modifications that can occur in OPSCC and their exploitation as potential biomarkers and therapeutic targets. Furthermore, we will address epigenetic alterations to OPSCC risk factors, with a particular focus on HPV infection, tobacco exposure, and heavy alcohol consumption.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  4. [해외논문]   Comparison of quantification algorithms for circulating cell-free DNA methylation biomarkers in blood plasma from cancer patients   SCIE

    de Vos, Luka (Department of Otolaryngology, University Hospital Bonn, Head and Neck Surgery, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Gevensleben, Heidrun (Institute of Pathology, University Hospital Bonn (UKB), ) , Schrö (Department of Otolaryngology, University Hospital Bonn, Head and Neck Surgery, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , ck, Andreas (Department of Otolaryngology, University Hospital Bonn, Head and Neck Surgery, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Franzen, Alina (Institute of Pathology, University Hospital Bonn (UKB), ) , Kristiansen, Glen (Department of Otolaryngology, University Hospital Bonn, Head and Neck Surgery, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Bootz, Friedrich (Department of Otolaryngology, University Hospital Bonn, Head and Neck Surgery, Sigmund-Freud-Str. 25, 53127 Bonn, Germany) , Dietrich, Dimo
    Clinical epigenetics v.9 no.1 ,pp. 125 , 2017 , 1868-7075 ,

    초록

    Background SHOX2 and SEPT9 methylation in circulating cell-free DNA (ccfDNA) in blood are established powerful and clinically valuable biomarkers for diagnosis, staging, prognosis, and monitoring of cancer patients. The aim of the present study was to evaluate different quantification algorithms (relative quantification, absolute quantification, quasi-digital PCR) with regard to their clinical performance. Methods Methylation analyses were performed in a training cohort (141 patients with head and neck squamous cell carcinoma [HNSCC], 170 control cases) and a testing cohort (137 HNSCC cases, 102 controls). DNA was extracted from plasma samples, bisulfite-converted, and analyzed via quantitative real-time PCR. SHOX2 and SEPT9 methylations were assessed separately and as panel [mean SEPT9 / SHOX2 ] using the ΔCT method for absolute quantification and the ΔΔCT-method for relative quantification. Quasi-digital PCR was defined as the number of amplification-positive PCR replicates. The diagnostic (sensitivity, specificity, area under the curve (AUC) of the receiver operating characteristic (ROC)) and prognostic accuracy (hazard ratio (HR) from Cox regression) were evaluated. Results Sporadic methylation in control samples necessitated the introduction of cutoffs resulting in 61–63% sensitivity/90–92% specificity ( SEPT9 /training), 53–57% sensitivity/87–90% specificity ( SHOX2 /training), and 64–65% sensitivity/90–91% specificity (mean SEPT9 / SHOX2 /training). Results were confirmed in a testing cohort with 54–56% sensitivity/88–90% specificity ( SEPT9 /testing), 43–48% sensitivity/93–95% specificity ( SHOX2 /testing), and 49–58% sensitivity/88–94% specificity (mean SEPT9 / SHOX2 /testing). All algorithms showed comparable cutoff-independent diagnostic accuracy with largely overlapping 95% confidence intervals ( SEPT9 : AUC training = 0.79&# 0.79–0.80; AUC testing = 0.74& 0.74–0.75; SHOX2 : AUC training = 0.78&# 0.78–0.81, AUC testing = 0.77& 0.77–0.79; mean SEPT9 / SHOX2 : AUC training = 0.81&# 0.81–0.84, AUC testing = 0.80) 0.80). The accurate prediction of overall survival was possible with all three algorithms (training cohort: HR SEPT9 = 1.2 1.23-1.90, HR SHOX2 = 1.1 1.14-1.85, HR mean SEPT9 / SHOX2 =1.19 1.19-1.89 ; testing cohort: HR SEPT9 =1.22 1.22-1.67, HR SHOX2 = 1.1 1.15-1.71, HR mean SEPT9 / SHOX2 = 1.1 1.12-1.77). Conclusion The concordant clinical performance based on different quantification algorithms allows for the application of various diagnostic platforms for the analysis of ccfDNA methylation biomarkers. Electronic supplementary material The online version of this article (10.1186/s13148-017-0425-4) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  5. [해외논문]   Feasibility of quantifying SDC2 methylation in stool DNA for early detection of colorectal cancer   SCIE

    Oh, Tae Jeong (Genomictree, Inc, 44-6 Techno 10-ro Yuseong-gu, Daejeon, 34027 South Korea ) , Oh, Hyun Il (Genomictree, Inc, 44-6 Techno 10-ro Yuseong-gu, Daejeon, 34027 South Korea ) , Seo, Yang Yei (Genomictree, Inc, 44-6 Techno 10-ro Yuseong-gu, Daejeon, 34027 South Korea ) , Jeong, Dongjun (Department of Pathology, College of Medicine, Soonchunhyang University, 23-20 Byeongmyeong-dong Dongnam-gu, Cheonan, Chungcheongnam-do 31151 South Korea ) , Kim, Changjin (Department of Pathology, College of Medicine, Soonchunhyang University, 23-20 Byeongmyeong-dong Dongnam-gu, Cheonan, Chungcheongnam-do 31151 South Korea ) , Kang, Hyoun Woo (Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, 27 Dongguk-ro Ilsandong-gu, Goyang-si, Gyeonggi-do 10326 South Korea ) , Han, Yoon Dae (Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro Seodaemun-gu, Seoul, 03722 South Korea ) , Chung, Hyun Cheol (Yonsei Cancer Center Yonsei University College of Medicine, 50-1 Yonsei-ro Seodaemun-gu, Seoul, 03722 South Korea ) , Kim, Nam Kyu (Department of Surgery, Yonsei University Coll) , An, Sungwhan
    Clinical epigenetics v.9 no.1 ,pp. 126 , 2017 , 1868-7075 ,

    초록

    Background Colorectal cancer (CRC) screening is the most efficient strategy to reduce disease-related mortality. Frequent aberrant DNA methylation is known to occur in selected genes and early during CRC development, which has emerged as a new epigenetic biomarker for early detection of CRC. Previously, we reported that we identified that CpG sites of SDC2 were aberrantly methylated in tumor tissues of most CRC patients through comprehensive methylation analysis and demonstrated a high potential of quantification of SDC2 methylation in blood for early detection of colorectal cancer. In this study, we aim to investigate the feasibility of quantifying SDC2 methylation in stool DNA for the early detection of CRC. The objective of this study was to confirm a high frequency of SDC2 methylation in tumor tissues at various stages of CRC and investigate the feasibility of a quantitative test for SDC2 methylation in fecal DNA by highly sensitive and accurate real-time PCR for early detection of CRC. Methods Bisulfite-pyrosequencing assay was performed to measure the SDC2 methylation status in tissue samples. For methylation analysis in stool DNA, a highly sensitive and accurate method was applied which implements consecutive two rounds of PCR consisting of unidirectional linear target enrichment (LTE) of SDC2 and quantitative methylation-specific real time PCR (qMSP) for SDC2 , named as me SDC2 LTE-qMSP assay. Its limit of detection was 0.1% methylation (corresponding to ~ 6 copies in total ~ 6200 genome copies). Results Positive SDC2 methylation was observed in 100% of primary tumors, 90.6% of adenomatous polyps, 94.1% of hyperplastic polyps, and 0% of normal tissues. SDC2 methylation level also significantly ( P SDC2 methylation by LTE-qMSP comparing CRC patients with various stages (I to IV) ( n = 50) and precancerous lesions ( n = 21) with healthy subjects ( n = 22), the overall sensitivity was 90.0% for detecting CRC and 33.3% for detecting small polyps, with a specificity of 90.9%. Conclusions Taken together, our result indicates that stool DNA-based SDC2 methylation test by LTE-qMSP is a potential noninvasive diagnostic tool for early detection of CRC.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  6. [해외논문]   Association between long interspersed nuclear element-1 methylation levels and relapse in Wilms tumors   SCIE

    de Sá (Post Graduate Program of Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil ) , Pereira, Bruna M. (Post Graduate Program of Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil ) , Montalvã (Pathology Division of Instituto Nacional do Câncer (DIPAT-INCA), Rua Cordeiro da Graça 156, Santo Cristo, Rio de Janeiro, 20220-400 Brazil ) , o-de-Azevedo, Rafaela (Post Graduate Program of Instituto Nacional do Cancer (INCA), Rio de Janeiro, Brazil ) , Faria, Paulo Antô (Molecular Carcinogenesis Program, Research Center (CPQ), Instituto Nacional do Câncer (INCA), Rua André) , nio (Cavalcanti 37, Centro, Rio de Janeiro, 20231-050 Brazil ) , de Paula Silva, Neimar (Brazilian Center for Research in Energy and Materials (CNPEM), Brazilian Biosciences National Laboratory (LNBio), Rua Giuseppe Máximo Scolfaro 10.000, Bosque das Palmeiras, Campinas, Sao Paulo 13083-970 Brazil ) , Nicolau-Neto, Pedro (Pediatric Hematology-Oncology Research Program, Research Center (CPQ), Instituto Nacional de Câncer (INCA), Rua Andre Cavalcanti 37, Centro, Rio de Janeiro, 20231-050 Brazil ) , Maschietto, Mariana (Molecular) , de Camargo, Beatriz , Soares Lima, Sheila Coelho
    Clinical epigenetics v.9 no.1 ,pp. 128 , 2017 , 1868-7075 ,

    초록

    Background Wilms tumor (WT) is a curable pediatric renal malignancy, but there is a need for new molecular biomarkers to improve relapse risk-directed therapy. Somatic alterations occur at relatively low frequencies whereas epigenetic changes at 11p15 are the most common aberration. We analyzed long interspersed element-1 (LINE-1) methylation levels in the blastemal component of WT and normal kidney samples to explore their prognostic significance. Results WT samples presented a hypomethylated pattern at all five CpG sites compared to matched normal kidney samples; therefore, the averaged methylation levels of the five CpG sites were used for further analyses. WT presented a hypomethylation profile (median 65.0%, 47.4–73.2%) compared to normal kidney samples (median 71.8%, 51.5–77.5%; p p = 0.0005), and a receiving operating characteristic curve analysis was applied to verify the ability of LINE-1 methylation levels to discriminate WT samples from these patients. Using a cut-off value of 62.71% for LINE-1 methylation levels, the area under the curve was 0.808, with a sensitivity of 76.5% and a specificity of 83.3%. Having identified differences in LINE-1 methylation between WT samples from patients with and without relapse in this cohort, we evaluated other prognostic factors using a logistic regression model. This analysis showed that in risk stratification, LINE-1 methylation level was an independent variable for relapse risk: the lower the methylation levels, the higher the risk of relapse. The logistic regression model indicated a relapse risk increase of 30% per decreased unit of methylation (odds ratio 1.30; 95% confidence interval 1.07–1.57). Conclusion Our results reinforce previous data showing a global hypomethylation profile in WT. LINE-1 methylation levels can be suggested as a marker of relapse after chemotherapy treatment in addition to risk classification, helping to guide new treatment approaches. Electronic supplementary material The online version of this article (10.1186/s13148-017-0431-6) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  7. [해외논문]   Targeted bisulfite sequencing identified a panel of DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC)   SCIE

    Pu, Weilin (State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China ) , Wang, Chenji (Department of Biochemistry and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu China ) , Chen, Sidi (State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China ) , Zhao, Dunmei (Department of Biochemistry and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu China ) , Zhou, Yinghui (Department of Biochemistry and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu China ) , Ma, Yanyun (Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China ) , Wang, Ying (Genesky Biotechnologies Inc., Shanghai, China ) , Li, Caihua (Genesky Biotechnologies Inc., Shanghai, China ) , Huang, Zebin (Genesky Biotechnologies Inc., S) , Jin, Li , Guo, Shicheng , Wang, Jiucun , Wang, Minghua
    Clinical epigenetics v.9 no.1 ,pp. 129 , 2017 , 1868-7075 ,

    초록

    Background DNA methylation has been implicated as a promising biomarker for precise cancer diagnosis. However, limited DNA methylation-based biomarkers have been described in esophageal squamous cell carcinoma (ESCC). Methods A high-throughput DNA methylation dataset (100 samples) of ESCC from The Cancer Genome Atlas (TCGA) project was analyzed and validated along with another independent dataset (12 samples) from the Gene Expression Omnibus (GEO) database. The methylation status of peripheral blood mononuclear cells and peripheral blood leukocytes from healthy controls was also utilized for biomarker selection. The candidate CpG sites as well as their adjacent regions were further validated in 94 pairs of ESCC tumor and adjacent normal tissues from the Chinese Han population using the targeted bisulfite sequencing method. Logistic regression and several machine learning methods were applied for evaluation of the diagnostic ability of our panel. Results In the discovery stage, five hyper-methylated CpG sites were selected as candidate biomarkers for further analysis as shown below: cg15830431, P = 2.20 × 10 −4 ; cg19396867, P = 3.60 × 10 −4 ; cg20655070, P = 3.60 × 10 −4 ; cg26671652, P = 5.77 × 10 −4 ; and cg27062795, P = 3.60 × 10 −4 . In the validation stage, the methylation status of both the five CpG sites and their adjacent genomic regions were tested. The diagnostic model based on the combination of these five genomic regions yielded a robust performance (sensitivity = 0.75, specificity = 0.88, AUC = 0.85). Eight statistical models along with five-fold cross-validation were further applied, in which the SVM model reached the best accuracy in both training and test dataset (accuracy = 0.82 and 0.80, respectively). In addition, subgroup analyses revealed a significant difference in diagnostic performance between the alcohol use and non-alcohol use subgroups. Conclusions Methylation profiles of the five genomic regions covering cg15830431 ( STK3 ), cg19396867, cg20655070, cg26671652 ( ZNF418 ), and cg27062795 ( ZNF542 ) can be used for effective methylation-based testing for ESCC diagnosis. Electronic supplementary material The online version of this article (10.1186/s13148-017-0430-7) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  8. [해외논문]   TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma and histologically normal tumor surrounding esophageal cells   SCIE

    Gonzaga, Isabela Martins (Programa de Carcinogênese Molecular, Instituto Nacional de Câncer, Coordenação de Pesquisa, Rua André) , Soares Lima, Sheila Coelho (Cavalcanti, 37–6° andar, Bairro de Fátima, Rio de Janeiro, Rio de Janeiro CEP: 20231-050 Brazil ) , Nicolau, Marina Chianello (Programa de Carcinogênese Molecular, Instituto Nacional de Câncer, Coordenação de Pesquisa, Rua André) , Nicolau-Neto, Pedro (Cavalcanti, 37–6° andar, Bairro de Fátima, Rio de Janeiro, Rio de Janeiro CEP: 20231-050 Brazil ) , da Costa, Nathalia Meireles (Programa de Carcinogênese Molecular, Instituto Nacional de Câncer, Coordenação de Pesquisa, Rua André) , de Almeida Simã (Cavalcanti, 37–6° andar, Bairro de Fátima, Rio de Janeiro, Rio de Janeiro CEP: 20231-050 Brazil ) , o, Tatiana (Programa de Carcinogênese Molecular, Instituto Nacional de Câncer, Coordenação de Pesquisa, Rua André) , Hernandez-Vargas, Hector (Cavalcanti, 37–6° andar, Bairro de Fátima, Rio de Janeiro, Rio de Janeiro CEP: 20231-050 Brazil ) , Herceg, Zdenko (Prog) , Ribeiro Pinto, Luis Felipe
    Clinical epigenetics v.9 no.1 ,pp. 130 , 2017 , 1868-7075 ,

    초록

    Background Esophageal squamous cell carcinoma (ESCC) is one of the 10 most incident cancer types in the world, and it is mainly associated with tobacco and alcohol consumption. ESCC mortality rates stand very close to its incidence, which is a direct consequence of a late diagnosis and an inefficient treatment. Although this scenery is quite alarming, the major molecular alterations that drive this carcinogenesis process remain unclear. We have previously shown through the first ESCC methylome analysis that TFF1 promoter is frequently hypermethylated in ESCC. Here, to evaluate TFF1 methylation as a potential biomarker of early ESCC diagnosis, we investigated the status of TFF1 promoter methylation and its expression in ESSC and histologically normal tumor surrounding tissue of ESCC patients in comparison to healthy esophagus of non-cancer individuals. Results Analysis of TFF1 promoter methylation, and gene and protein expression in 65 ESCC patients and 88 controls revealed that TFF1 methylation levels were already increased in histologically normal tumor surrounding tissue of ESCC patients when compared to healthy esophagus of non-cancer individuals. This increase in DNA methylation was followed by the reduction of TFF1 mRNA expression. Interestingly, TFF1 expression was capable of distinguishing tumor surrounding normal tissue from normal mucosa of healthy individuals with 92% accuracy. In addition, TFF1 protein was undetectable both in tumor and surrounding mucosa by immunohistochemistry, while submucosa glands of the healthy esophagus showed positive staining. Furthermore, treatment of TE-1 and TE-13 ESCC cell lines with decitabine led to a reduction of promoter methylation and consequent upregulation of TFF1 gene and protein expression. Finally, using TCGA data we showed that TFF1 loss is observed in ESCC, but not in esophageal adenocarcinoma, highlighting the different molecular mechanisms involved in the development of each histological subtype of esophageal cancer. Conclusions This study shows that TFF1 expression is silenced in early phases of ESCC development, which seems to be mediated at least in part by promoter hypermethylation, and provides the basis for the use of TFF1 expression as a potential biomarker for early ESCC detection. Electronic supplementary material The online version of this article (10.1186/s13148-017-0429-0) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  9. [해외논문]   Bronchial biopsy specimen as a surrogate for DNA methylation analysis in inoperable lung cancer   SCIE

    Um, Sang-Won (Department of Internal Medicine, Samsung Medical Center, Research Institute for Future Medicine, Sungkyunkwan University School of Medicine, Seoul, 135-710 Korea ) , Kim, Hong Kwan (Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710 Korea ) , Kim, Yujin (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 Korea ) , Lee, Bo Bin (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 Korea ) , Kim, Dongho (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746 Korea ) , Han, Joungho (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710 Korea ) , Kim, Hojoong (Department of Internal Medicine, Samsung Medical Center, Research Institute for Future Medicine, Sungkyunkwan University School of Medicine, Seoul) , Shim, Young Mog , Kim, Duk-Hwan
    Clinical epigenetics v.9 no.1 ,pp. 131 , 2017 , 1868-7075 ,

    초록

    Background This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy specimens using the Infinium HumanMethylation450 BeadChip, and models for prediction of lung cancer were evaluated using TCGA lung cancer data. Results Four thousand seven hundred and twenty-six CpGs ( P HOXA9 , SOX17 , ZNF154 , HOXD13 ); (ii) cell signaling ( HBP1 , SFRP1 , VIPR2 ); and (iii) adhesion ( PCDH17 , ITGA5 , CD34 ). Three logistic regression models based on the 10 CpGs classified 897 TCGA primary lung tissues with a sensitivity of 95.0~97.8% and a specificity of 97.4~98.7%. However, the classification performance of the models was very poor in bronchial washing samples: the area under the curve (AUC) was equal to 0.72~0.78. The methylation levels of the 10 CpGs in bronchial biopsy were not significantly different from those in surgically resected tumor tissues ( P > 0.05, Wilcoxon rank-sum test). However, their methylation levels were significantly different between paired bronchial biopsy and washing ( P Conclusions The present study suggests that bronchial biopsy specimen may be used as a surrogate for DNA methylation analysis in patient with inoperable lung cancer. Electronic supplementary material The online version of this article (10.1186/s13148-017-0432-5) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  10. [해외논문]   Lung function discordance in monozygotic twins and associated differences in blood DNA methylation   SCIE

    Bolund, Anneli C. S. (Department of Public Health, Section for Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark ) , Starnawska, Anna (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark ) , Miller, Martin R. (Institute of Occupational and Environmental Medicine, University of Birmingham, Birmingham, UK ) , Schlü (Department of Public Health, Section for Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark ) , nssen, Vivi (Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark ) , Backer, Vibeke (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark ) , Børglum, Anders D. (The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark ) , Christensen, Kaare (The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark ) , Tan, Qihua (The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark ) , Christiansen, Lene (Department of Public Health) , Sigsgaard, Torben
    Clinical epigenetics v.9 no.1 ,pp. 132 , 2017 , 1868-7075 ,

    초록

    Background Lung function is an important predictor of morbidity and mortality, with accelerated lung function decline reported to have immense consequences for the world's healthcare systems. The lung function decline across individual's lifetime is a consequence of age-related changes in lung anatomical structure and combination of various environmental factors; however, the exact molecular mechanisms contributing to this decline are not fully understood. DNA methylation is an epigenetic modification that changes across individual's lifetime, as well as allows for interplay between environmental and genetic factors. DNA methylation plays a crucial role in regulation of gene expression, with increasing evidence linking aberrant DNA methylation levels with a number of common human diseases. In this study, we investigated possible associations between genome-wide DNA methylation levels and lung function in 169 pairs of middle-aged monozygotic twins (86 male pairs: mean age (min-max) = 66 years (57–79); 83 female pairs: mean age (min-max) = 66 years (56–78)). The twins were collected from the Danish Twin Registry and were examined at baseline (1998–1999) and follow-up (2008–2011) visits. Using the twin design, we correlated intra-pair differences in cross-sectional and longitudinal lung function with intra-pair blood DNA methylation differences at follow-up by linear regression analyses adjusted for sex, age, BMI, smoking, and blood cell composition measured for each individual with the use of flow cytometry. Results We identified several differentially methylated CpG sites associated with forced expiratory volume the first second (FEV1) and forced vital capacity (FVC). Three probes identified for level of FVC were located in GLIPR1L2 gene (lowest p value = 7.14 × 10−8), involved in innate immunity and tumour-suppressor/pro-oncogenic mechanisms. Change in FEV1 during the 11-year follow-up period was associated with blood DNA methylation level in TRIM27 gene ( p value = 1.55 × 10 −6 ), a negative regulator of CD4 T cells, and also involved in cancer development. Several enriched pathways were identified, especially for FEV1, with one being “TGFBR” (Benjamini-Hochberg adj p value = 0.045), the receptor for TGFβ, a growth factor involved in normal lung tissue repair through pro-fibrotic effects. Conclusions Our findings suggest that epigenetic regulation of immunological- and cancer-related genes, as well as TGF-β-receptor-related genes, may be involved in the cross-sectional level and longitudinal change in lung function in middle-aged monozygotic twins. Electronic supplementary material The online version of this article (10.1186/s13148-017-0427-2) contains supplementary material, which is available to authorized users.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지

논문관련 이미지