5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers
DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could...
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| Published in | Cell research Vol. 27; no. 10; pp. 1243 - 1257 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.10.2017
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA （cfDNA） and in genomic DNA （gDNA） of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liv- er or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of cir- culating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples. |
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| AbstractList | DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples. DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA （cfDNA） and in genomic DNA （gDNA） of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liv- er or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of cir- culating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples. DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples. |
| Author | Wenshuai Li;Xu Zhang;Xingyu Lu;Lei You;Yanqun Song;Zhongguang Luo;Jun Zhang;Ji Nie;Wanwei Zheng;Diannan Xu;Yaping Wang;Yuanqiang Dong;Shulin Yu;Jun Hong;Jianping Shi;Hankun Hao;Fen Luo;Luchun Hua;Peng Wang;Xiaoping Qian;Fang Yuan;Lianhuan Wei;Ming Cui;Taiping Zhang;Quan Liao;Menghua Dai;Ziwen Liu;Ge Chen;Katherine Meckel;Sarbani Adhikari;Guifang Jia;Marc B Bissonnette;Xinxiang Zhang;Yupei Zhao;Wei Zhang;Chuan He;Jie Liu |
| AuthorAffiliation | Department of Digestive Diseases, Huashan Hospital Fudan University, Shanghai 200040, China;Section of Hematology/Oncology, Department of Medicine, University of Illinois, Chicago, IL 60612, USA;Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA;Shanghai Epican Genetech, Co. Ltd., Zhangjiang Hi-Tech Park, Shanghai 201203, China;Department of General Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences, Beijing 100730, China;Department of General Surgery, Huashan Hospital Fudan University, Shanghai 200040, China;Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China;Department of Digestive Diseases, Pudong Hospital Fudan University, Shanghai 201399, China;Department of Oncology, Nanjing Drum Tower Hospital Nanjing University Medical School Nanjing 210008, China;Beijin |
| Author_xml | – sequence: 1 givenname: Wenshuai surname: Li fullname: Li, Wenshuai organization: Department of Digestive Diseases, Huashan Hospital, Fudan University – sequence: 2 givenname: Xu surname: Zhang fullname: Zhang, Xu organization: Department of Medicine, Section of Hematology/Oncology, University of Illinois – sequence: 3 givenname: Xingyu surname: Lu fullname: Lu, Xingyu organization: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Shanghai Epican Genetech, Co. Ltd – sequence: 4 givenname: Lei surname: You fullname: You, Lei organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 5 givenname: Yanqun surname: Song fullname: Song, Yanqun organization: Shanghai Epican Genetech, Co. Ltd – sequence: 6 givenname: Zhongguang surname: Luo fullname: Luo, Zhongguang organization: Department of Digestive Diseases, Huashan Hospital, Fudan University – sequence: 7 givenname: Jun surname: Zhang fullname: Zhang, Jun organization: Department of Digestive Diseases, Huashan Hospital, Fudan University – sequence: 8 givenname: Ji surname: Nie fullname: Nie, Ji organization: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago – sequence: 9 givenname: Wanwei surname: Zheng fullname: Zheng, Wanwei organization: Department of Digestive Diseases, Huashan Hospital, Fudan University – sequence: 10 givenname: Diannan surname: Xu fullname: Xu, Diannan organization: Department of Digestive Diseases, Huashan Hospital, Fudan University – sequence: 11 givenname: Yaping surname: Wang fullname: Wang, Yaping organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 12 givenname: Yuanqiang surname: Dong fullname: Dong, Yuanqiang organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 13 givenname: Shulin surname: Yu fullname: Yu, Shulin organization: Department of Integrative Oncology, Shanghai Cancer Center, Fudan University – sequence: 14 givenname: Jun surname: Hong fullname: Hong, Jun organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 15 givenname: Jianping surname: Shi fullname: Shi, Jianping organization: Department of Digestive Diseases, Pudong Hospital, Fudan University – sequence: 16 givenname: Hankun surname: Hao fullname: Hao, Hankun organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 17 givenname: Fen surname: Luo fullname: Luo, Fen organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 18 givenname: Luchun surname: Hua fullname: Hua, Luchun organization: Department of General Surgery, Huashan Hospital, Fudan University – sequence: 19 givenname: Peng surname: Wang fullname: Wang, Peng organization: Department of Integrative Oncology, Shanghai Cancer Center, Fudan University – sequence: 20 givenname: Xiaoping surname: Qian fullname: Qian, Xiaoping organization: Department of Oncology, Nanjing Drum Tower Hospital, Nanjing University Medical School – sequence: 21 givenname: Fang surname: Yuan fullname: Yuan, Fang organization: Beijing National Laboratory for Molecular Sciences, College of Chemistry, Peking University, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University – sequence: 22 givenname: Lianhuan surname: Wei fullname: Wei, Lianhuan organization: Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University – sequence: 23 givenname: Ming surname: Cui fullname: Cui, Ming organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 24 givenname: Taiping surname: Zhang fullname: Zhang, Taiping organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 25 givenname: Quan surname: Liao fullname: Liao, Quan organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 26 givenname: Menghua surname: Dai fullname: Dai, Menghua organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 27 givenname: Ziwen surname: Liu fullname: Liu, Ziwen organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 28 givenname: Ge surname: Chen fullname: Chen, Ge organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 29 givenname: Katherine surname: Meckel fullname: Meckel, Katherine organization: Department of Medicine, The University of Chicago – sequence: 30 givenname: Sarbani surname: Adhikari fullname: Adhikari, Sarbani organization: Department of Medicine, The University of Chicago – sequence: 31 givenname: Guifang surname: Jia fullname: Jia, Guifang organization: Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Department of Chemical Biology, Structure and Function Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University – sequence: 32 givenname: Marc B surname: Bissonnette fullname: Bissonnette, Marc B organization: Department of Medicine, The University of Chicago – sequence: 33 givenname: Xinxiang surname: Zhang fullname: Zhang, Xinxiang organization: Beijing National Laboratory for Molecular Sciences, College of Chemistry, Peking University, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University – sequence: 34 givenname: Yupei surname: Zhao fullname: Zhao, Yupei organization: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences – sequence: 35 givenname: Wei surname: Zhang fullname: Zhang, Wei email: wei.zhang1@northwestern.edu organization: Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine – sequence: 36 givenname: Chuan surname: He fullname: He, Chuan email: chuanhe@uchicago.edu organization: Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Beijing National Laboratory for Molecular Sciences, College of Chemistry, Peking University – sequence: 37 givenname: Jie surname: Liu fullname: Liu, Jie email: jieliu@fudan.edu.cn organization: Department of Digestive Diseases, Huashan Hospital, Fudan University, Department of Immunology, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28925386$$D View this record in MEDLINE/PubMed |
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| Keywords | 5hmC-Seal cancer biomarker liquid biopsy 5-hydroxymethylcytosine circulating cell-free DNA |
| Language | English |
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| Notes | DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA （cfDNA） and in genomic DNA （gDNA） of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liv- er or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of cir- culating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples. 5-hydroxymethylcytosine; liquid biopsy; circulating cell-free DNA; cancer biomarker; 5hmC-Seal 31-1568 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These four authors contributed equally to this work. |
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| PublicationTitle | Cell research |
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| Snippet | DNA modifications such as 5-methylcytosine （5mC） and 5-hydroxymethylcytosine （5hmC） are epigenetic marks known to affect global gene efpression in mammals.... DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals.... |
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| SubjectTerms | 5-Methylcytosine - analogs & derivatives 5-Methylcytosine - blood 5-甲基胞嘧啶 631/67/1857 692/53/2421 692/699/1503/1504 692/700/1750 Adolescent Adult Aged Biomarkers Biomarkers, Tumor - blood Cancer Cell Biology Cell-Free Nucleic Acids - blood Cell-Free Nucleic Acids - genetics Chromatin Circulating Tumor DNA - blood Colorectal cancer Deoxyribonucleic acid Diagnosis Diagnostic systems DNA DNA Methylation - genetics DNA修饰 Epigenetics Epigenomics Female Gastric cancer Gene expression Gene Expression Regulation, Neoplastic - genetics Genomes Humans Life Sciences Liquid Biopsy Liver Liver cancer Male Middle Aged Neoplasms - blood Neoplasms - classification Neoplasms - genetics Neoplasms - pathology Original original-article Pancreas Pancreatic cancer Thyroid Thyroid cancer Transcription Young Adult 人类基因组 生物标志物 癌症 签名 羟甲基 诊断 |
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| Title | 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers |
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