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Clinical epigenetics 130건

  1. [해외논문]   The immunomodulatory anticancer agent, RRx-001, induces an interferon response through epigenetic induction of viral mimicry   SCIE

    Zhao, Hongjuan (Department of Urology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 USA ) , Ning, Shoucheng (Department of Radiation Oncology, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305 USA ) , Nolley, Rosalie (Department of Urology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 USA ) , Scicinski, Jan (EpicentRx, Inc., 800W El Camino Real, Suite 180, Mountain View, CA 94040 USA ) , Oronsky, Bryan (EpicentRx, Inc., 800W El Camino Real, Suite 180, Mountain View, CA 94040 USA ) , Knox, Susan J. (Department of Radiation Oncology, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305 USA ) , Peehl, Donna M. (Department of Urology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305 USA)
    Clinical epigenetics v.9 no.1 ,pp. 4 , 2017 , 1868-7075 ,

    초록

    Background RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies. Here, we identified another mechanism, viral mimicry, which refers to the “unsilencing” of epigenetically repressed viral genes present in the tumor that provokes an immune response and may contribute to the anticancer activity of RRx-001. Results RRx-001 inhibited the growth of colon cancer cells (HCT 116) and decreased levels of the DNA methyltransferases DNMT1 and DNMT3a in a time and dose-dependent manner. Treatment of HCT 116 cells with 0.5 μM RRx-001 for 24 h significantly increased transcripts of interferon (IFN)-responsive genes and this induction was sustained for up to 4 weeks after transient exposure to RRx-001. ELISA assays showed that RRx-001 increased secretion of type I and III IFNs by HCT 116 cells, and these IFNs were confirmed to be bioactive. Transcription of endogenous retrovirus ERV-Fc2 and LTRs from the ERV-L family (MLT2B4 and MLT1C49) was induced by RRx-001. The induction of ERV-Fc2-env was through demethylation of ERV-Fc2 LTR as determined by methylation-specific polymerase chain reaction and combined bisulfite restriction analysis. Immunofluorescence staining with J2 antibody confirmed induction of double-stranded RNA. Conclusions Transient exposure of HCT 116 cells to low-dose RRx-001 induced transcription of silenced retroviral genes present in the cancer cell DNA with subsequent synthesis of IFN in response to this “pseudo-pathogenic” stimulus, mimicking an antiviral defense. RRx-001-mediated IFN induction may have the potential to improve the efficacy of immunotherapies as well as radiotherapy, standard chemotherapies and molecularly targeted agents when used in combination. The striking safety profile of RRx-001 in comparison to other more toxic epigenetic and immunomodulatory agents such as azacitidine makes it a leading candidate for such clinical applications.

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  2. [해외논문]   The epigenomic basis of common diseases   SCIE

    Rodger, Euan J. (Department of Pathology, Dunedin School of Medicine, University of Otago, Hanover Street, P.O. Box 56, Dunedin, 9054 New Zealand ) , Chatterjee, Aniruddha (Department of Pathology, Dunedin School of Medicine, University of Otago, Hanover Street, P.O. Box 56, Dunedin, 9054 New Zealand)
    Clinical epigenetics v.9 no.1 ,pp. 5 , 2017 , 1868-7075 ,

    초록

    A report of the 6 th Epigenomics of Common Diseases Conference held at the Wellcome Genome Campus in Hinxton, Cambridge, UK, on 1–4 November 2016.

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  3. [해외논문]   Epigenome-wide association study of DNA methylation in panic disorder   SCIE

    Shimada-Sugimoto, Mihoko (Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo Ward, Tokyo, 113-0033 Japan ) , Otowa, Takeshi (Graduate School of Clinical Psychology, Teikyo Heisei University Major of Professional Clinical Psychology, 2-51-4 Higashiikebukuro, Toshima Ward, Tokyo, 171-0014 Japan ) , Miyagawa, Taku (Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo Ward, Tokyo, 113-0033 Japan ) , Umekage, Tadashi (Division for Environment, Health and Safety, The University of Tokyo, 7-3-1 Hongo, Bunkyo Ward, Tokyo, 113-0033 Japan ) , Kawamura, Yoshiya (Department of Psychiatry, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura City, Kanagawa 247-8533 Japan ) , Bundo, Miki (Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto 860-8556 Japan ) , Iwamoto, Kazuya (Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo Ward, Kumamoto City, Kumamoto 860-8556 Japan ;) , Tochigi, Mamoru , Kasai, Kiyoto , Kaiya, Hisanobu , Tanii, Hisashi , Okazaki, Yuji , Tokunaga, Katsushi , Sasaki, Tsukasa
    Clinical epigenetics v.9 no.1 ,pp. 6 , 2017 , 1868-7075 ,

    초록

    Background Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD. Methods The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 48, control, N = 48) extracted from peripheral blood. Methylation arrays were used for the analysis. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β values were converted to M values via the logit transformation for epigenome-wide association study. The relationship between each DNA methylation site and PD was assessed by linear regression analysis with adjustments for the effects of leukocyte subsets. Results Forty CpG sites showed significant association with PD at 5% FDR correction, though the differences of the DNA methylation levels were relatively small. Most of the significant CpG sites (37/40 CpG sites) were located in or around CpG islands. Many of the significant CpG sites (27/40 CpG sites) were located upstream of genes, and all such CpG sites with the exception of two were hypomethylated in PD subjects. A pathway analysis on the genes annotated to the significant CpG sites identified several pathways, including “positive regulation of lymphocyte activation.” Conclusions Although future studies with larger number of samples are necessary to confirm the small DNA methylation abnormalities associated with PD, there is a possibility that several CpG sites might be associated, together as a group, with PD. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0307-1) contains supplementary material, which is available to authorized users.

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  4. [해외논문]   CDH22 hypermethylation is an independent prognostic biomarker in breast cancer   SCIE

    Martí (Cancer Epigenetics Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Irunlarrea Road, 3, 31008 Pamplona, Spain ) , n-Sá (Cancer Epigenetics Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Irunlarrea Road, 3, 31008 Pamplona, Spain ) , nchez, Esperanza (Cancer Epigenetics Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Irunlarrea Road, 3, 31008 Pamplona, Spain ) , Mendaza, Saioa (Cancer Epigenetics Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Irunlarrea Road, 3, 31008 Pamplona, Spain ) , Ulazia-Garmendia, Ane (Department of Pathology, Complejo Hospitalario de Navarra, Irunlarrea Road, 3, 31008 Pamplona, Spain ) , Monreal-Santesteban, Iñ (Department of Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain ) , aki (Immunomodulation Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Pamplona, Spain ) , Có (Department of Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Spain ) , rdoba, Alicia (Biobank of Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Pamplona, Spain ) , Vicente-Garcí (Cancer Epigenetics Group, Navarrabiomed. Departmento de Salud-UPNA. IdiSNA, Irunlarrea) , a, Francisco , Blanco-Luquin, Idoia , De La Cruz, Susana , Aramendia, Ana , Guerrero-Setas, David
    Clinical epigenetics v.9 no.1 ,pp. 7 , 2017 , 1868-7075 ,

    초록

    Background Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose of our study was to determine the molecular status and clinical value of CDH22 in BC. Results We observed by immunohistochemistry that the level of CDH22 expression was lower in BC tissues than in their matched adjacent-to-tumour and non-neoplastic tissues from reduction mammoplasties. Since epigenetic alteration is one of the main causes of gene silencing, we analysed the hypermethylation of 3 CpG sites in the CDH22 promoter by pyrosequencing in a series of 142 infiltrating duct BC cases. CDH22 was found to be hypermethylated in tumoral tissues relative to non-neoplastic mammary tissues. Importantly, this epigenetic alteration was already present in adjacent-to-tumour tissues, although to a lesser extent than in tumoral samples. Furthermore, CDH22 gene regulation was dynamically modulated in vitro by epigenetic drugs. Interestingly, CDH22 hypermethylation in all 3 CpG sites simultaneously, but not expression, was significantly associated with shorter progression-free survival ( p = 0.015) and overall survival ( p = 0.021) in our patient series. Importantly, CDH22 hypermethylation was an independent factor that predicts poor progression-free survival regardless of age and stage ( p = 0.006). Conclusions Our results are the first evidence that CDH22 is hypermethylated in BC and that this alteration is an independent prognostic factor in BC. Thus, CDH22 hypermethylation could be a potential biomarker of poor prognosis in BC. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0309-z) contains supplementary material, which is available to authorized users.

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  5. [해외논문]   UroMark—a urinary biomarker assay for the detection of bladder cancer   SCIE

    Feber, Andrew (UCL Cancer Institute, University College London, London, UK ) , Dhami, Pawan (UCL Cancer Institute, University College London, London, UK ) , Dong, Liqin (UCL Cancer Institute, University College London, London, UK ) , de Winter, Patricia (Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK ) , Tan, Wei Shen (Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK ) , Martí (Molecular Oncology Unit, CIEMAT (ed70A), Madrid, Spain & Biomedical Research Institute I+12, Universitary Hospistal 12 de Octubre, Av Cordoba s/n. 28041, Madrid, Spain ) , nez-Ferná (UCL Cancer Institute, University College London, London, UK ) , ndez, Mó (Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK ) , nica (UCL Cancer Institute, University College London, London, UK ) , Paul, Dirk S. (Division of Surgery & Interventional Science, UCL Medical School, University College London, London, UK ) , Hynes-Allen, Antony (Division of Surgery & Interventional Science, UCL Medical School, University College London, Lon) , Rezaee, Sheida , Gurung, Pratik , Rodney, Simon , Mehmood, Ahmed , Villacampa, Felipe , de la Rosa, Federico , Jameson, Charles , Cheng, Kar Keung , Zeegers, Maurice P. , Bryan, Richard T. , James, Nicholas D. , Paramio, Jesus M. , Freeman, Alex , Beck, Stephan , Kelly, John D.
    Clinical epigenetics v.9 no.1 ,pp. 8 , 2017 , 1868-7075 ,

    초록

    Background Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. Results We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort ( n = 274, non-cancer ( n = 167) and bladder cancer ( n = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. Conclusions Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0303-5) contains supplementary material, which is available to authorized users.

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  6. [해외논문]   Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging   SCIE

    Zhang, Yan (Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany ) , Hapala, Jan (Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany ) , Brenner, Hermann (Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581/TP4, 69120 Heidelberg, Germany ) , Wagner, Wolfgang (Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, University Hospital of the RWTH Aachen, Pauwelsstrasse 20, 52074 Aachen, Germany)
    Clinical epigenetics v.9 no.1 ,pp. 9 , 2017 , 1868-7075 ,

    초록

    Background There is a growing interest in simple molecular biomarkers for biological aging. Age-associated DNA methylation (DNAm) changes at specific CG dinucleotides can be combined into epigenetic age predictors to estimate chronological age—and the deviation of chronological and predicted age (∆ age ) seems to be associated with all-cause mortality. In this study, we have further validated this association and analyzed whether or not individual age-associated CG-dinucleotides (CpGs) are related to life expectancy. Findings In the German ESTHER cohort, we used 864 DNAm profiles of blood samples as the discovery set and 1000 DNAm profiles as the validation set to predict chronological age with three previously reported age predictors—based on 99, 71, or 353 age-associated CpGs. Several of these individual CpGs were significantly associated with life expectancy, and for some of these CpGs, this was even reproducible in the independent datasets. Notably, those CpGs that revealed significant association with life expectancy were overall rather hypomethylated upon aging. Conclusion Individual age-associated CpGs may provide biomarkers for all-cause mortality—but confounding factors need to be critically taken into consideration, and alternative methods, which facilitate more quantitative measurements at individual CpGs, might be advantageous. Our data suggest that particularly specific CpGs that become hypomethylated upon aging are indicative of biological aging. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0315-9) contains supplementary material, which is available to authorized users.

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  7. [해외논문]   Immunomethylomic approach to explore the blood neutrophil lymphocyte ratio (NLR) in glioma survival   SCIE

    Wiencke, John K. (Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158-0520 USA ) , Koestler, Devin C. (Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS 66160 USA ) , Salas, Lucas A. (Computational Biology Core, University of California San Francisco, San Francisco, CA 94158 USA ) , Wiemels, Joseph L. (Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158 USA ) , Roy, Ritu P. (Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158 USA ) , Hansen, Helen M. (Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158-0520 USA ) , Rice, Terri (Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158-0520 USA ) , McCoy, Lucie S. (Department of Neurological Surgery, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94158-0520 USA ) , Bracci, Paige M. (Department of Epidemiology and Biostatistics, University of C) , Molinaro, Annette M. , Kelsey, Karl T. , Wrensch, Margaret R. , Christensen, Brock C.
    Clinical epigenetics v.9 no.1 ,pp. 10 , 2017 , 1868-7075 ,

    초록

    Background Differentially methylated regions (DMRs) within DNA isolated from whole blood can be used to estimate the proportions of circulating leukocyte subtypes. We use the term “immunomethylomics” to describe the application of these immune lineage DMRs to studying leukocyte profiles. Here, we applied this approach to peripheral blood DNA from 72 glioma patients with molecularly defined brain tumors, representing common patient groups with defined characteristic survival times and risk factors. We first estimated the proportions of leukocyte subtypes in samples using deconvolution algorithms with reference DMR libraries from isolated leukocyte populations and Illumina 450K DNA methylation data. Then, we calculated the neutrophil to lymphocyte ratio (NLR) using methylation-derived cell composition estimates (mdNLR). The NLR is considered an indicator of immunosuppressive cells in cancer patients. Results Elevated mdNLR scores were observed in glioma patients compared to mdNLR values of published controls. Significantly decreased survival times were associated with mdNLR ≥ 4.0 in Cox proportional hazards models adjusted for age, gender, tumor grade, and molecular subtype (HR 2.02, 95% CI, 1.11–3.69). We also identified five myeloid-related CpGs that were highly correlated with the mdNLR (adjusted R 2 ≥ 0.80). Each of the five myeloid CpG loci was associated with survival when adjusted for the above covariates and offer a simplified approach for utilizing fresh or archived peripheral blood samples for interrogating a very small number of methylation markers to estimate myeloid immune influences in glioma survival. Conclusions The mdNLR (based on DNA methylation) is a novel candidate methylation biomarker that represents immunosuppressive myeloid cells within the blood of glioma patients with potential application in clinical trials and future epidemiologic studies of glioma risk and survival. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0316-8) contains supplementary material, which is available to authorized users.

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  8. [해외논문]   An empirically driven data reduction method on the human 450K methylation array to remove tissue specific non-variable CpGs   SCIE

    Edgar, Rachel D. (Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada ) , Jones, Meaghan J. (Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada ) , Robinson, Wendy P. (Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada ) , Kobor, Michael S. (Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada)
    Clinical epigenetics v.9 no.1 ,pp. 11 , 2017 , 1868-7075 ,

    초록

    Background Population based epigenetic association studies of disease and exposures are becoming more common with the availability of economical genome-wide technologies for interrogation of the methylome, such as the Illumina 450K Human Methylation Array (450K). Often, the expected small number of differentially methylated cytosine-guanine pairs (CpGs) in studies of the human methylome presents a statistical challenge, as the large number of CpGs measured on the 450K necessitates careful multiple test correction. While the 450K is a highly useful tool for population epigenetic studies, many of the CpGs tested are not variable and thus of limited information content in the context of the study and tissue. CpGs with observed lack of variability in the tissue under study could be removed to reduce the data dimensionality, limit the severity of multiple test correction and allow for improved detection of differential DNA methylation. Methods Here, we performed a meta-analysis of 450K data from three commonly studied human tissues, namely blood (605 samples), buccal epithelial cells (121 samples) and placenta (157 samples). We developed lists of CpGs that are non-variable in each tissue. Results These lists are surprisingly large (blood 114,204 CpGs, buccal epithelial cells 120,009 CpGs and placenta 101,367 CpGs) and thus will be valuable filters for epigenetic association studies, considerably reducing the dimensionality of the 450K and subsequently the multiple testing correction severity. Conclusions We propose this empirically derived method for data reduction to allow for more power in detecting differential DNA methylation associated with exposures in studies on the human methylome. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0320-z) contains supplementary material, which is available to authorized users.

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  9. [해외논문]   PITX3 DNA methylation is an independent predictor of overall survival in patients with head and neck squamous cell carcinoma   SCIE

    Sailer, Verena (Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY USA ) , Holmes, Emily Eva (Institute of Pathology, University Hospital Bonn, Bonn, Germany ) , Gevensleben, Heidrun (Institute of Pathology, University Hospital Bonn, Bonn, Germany ) , Goltz, Diane (Institute of Pathology, University Hospital Cologne, Cologne, Germany ) , Drö (Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ) , ge, Freya (Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Franzen, Alina (Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Dietrich, Jö (Institute of Pathology, University Hospital Bonn, Bonn, Germany ) , rn (Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Kristiansen, Glen (Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany ) , Bootz, Friedrich (Department of Otolaryngology, Hea) , Schrö , ck, Andreas , Dietrich, Dimo
    Clinical epigenetics v.9 no.1 ,pp. 12 , 2017 , 1868-7075 ,

    초록

    Background Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 ( PITX3 ) was evaluated in HNSCC. Methods Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort). The results were validated with Infinium HumanMethylation450 BeadChip data from a 528 HNSCC patient cohort (validation cohort) generated by The Cancer Genome Atlas (TCGA) Research Network. Results PITX3 methylation was significantly higher methylated in tumor compared to normal adjacent tissue (NAT; training cohort: median methylation NAT 32.3%, tumor 71.8%, p p PITX3 methylation was also significantly correlated with lymph node status both in the training ( p = 0.006) and validation ( p PITX3 methylation was significantly higher in HPV-associated (p16-positive) tumors compared to p16-negative tumors (training cohort: 73.7 vs. 66.2%, p = 0.013; validation cohort: 40.0 vs. 33.1%, p = 0.015). Hypermethylation was significantly associated with the risk of death (training cohort: hazard ratio (HR) = 1.80, [95% confidence interval (CI) 1.20–2.69], p = 0.005; validation cohort: HR = 1.43, [95% CI 1.05–1.95], p = 0.022). In multivariate Cox analyses, PITX3 added independent prognostic information. Messenger RNA (mRNA) expression analysis revealed an inverse correlation with PITX3 methylation in the TCGA cohort. Conclusions PITX3 DNA methylation is an independent prognostic biomarker for overall survival in patients with HNSCC and might aid in the process of risk stratification for individualized treatment.

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    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.

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  10. [해외논문]   Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India   SCIE

    Basu, Baidehi (Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India ) , Chakraborty, Joyeeta (Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India ) , Chandra, Aditi (Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India ) , Katarkar, Atul (Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India ) , Baldevbhai, Jadav Ritesh Kumar (Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India ) , Dhar Chowdhury, Debjit (Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India ) , Ray, Jay Gopal (Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India ) , Chaudhuri, Keya (Molecular Genetics Division, CSIR-Indian Institute of Chemical biology, 4 Raja S C Mullick Road, Kolkata, 700 032 India ) , Chatterjee, Raghunath (Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India)
    Clinical epigenetics v.9 no.1 ,pp. 13 , 2017 , 1868-7075 ,

    초록

    Background Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples. Results Genome-wide DNA methylation analysis identified several novel differentially methylated regions associated with OSCC. Hypermethylation is primarily enriched in the CpG-rich regions, while hypomethylation is mainly in the open sea. Distinct epigenetic drifts for hypo- and hypermethylation across CpG islands suggested independent mechanisms of hypo- and hypermethylation in OSCC development. Aberrant DNA methylation in the promoter regions are concomitant with gene expression. Hypomethylation of immune genes reflect the lymphocyte infiltration into the tumor microenvironment. Comparison of methylome data with 312 TCGA HNSCC samples identified a unique set of hypomethylated promoters among the OSCC patients in India. Pathway analysis of unique hypomethylated promoters indicated that the OSCC patients in India induce an anti-tumor T cell response, with mobilization of T lymphocytes in the neoplastic environment. Survival analysis of these epigenetically regulated immune genes suggested their prominent role in OSCC progression. Conclusions Our study identified a unique set of hypomethylated regions, enriched in the promoters of immune response genes, and indicated the presence of a strong immune component in the tumor microenvironment. These methylation changes may serve as potential molecular markers to define risk and to monitor the prognosis of OSCC patients in India. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0314-x) contains supplementary material, which is available to authorized users.

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    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.

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