Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma
An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive ‘liquid biopsy’ for diagnosis and monitoring of cancer. He...
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| creator | Xu, Rui-hua Wei, Wei Krawczyk, Michal Wang, Wenqiu Luo, Huiyan Flagg, Ken Yi, Shaohua Shi, William Quan, Qingli Li, Kang Zheng, Lianghong Zhang, Heng Caughey, Bennett A. Zhao, Qi Hou, Jiayi Zhang, Runze Xu, Yanxin Cai, Huimin Li, Gen Hou, Rui Zhong, Zheng Lin, Danni Fu, Xin Zhu, Jie Duan, Yaou Yu, Meixing Ying, Binwu Zhang, Wengeng Wang, Juan Zhang, Edward Zhang, Charlotte Li, Oulan Guo, Rongping Carter, Hannah Zhu, Jian-kang Hao, Xiaoke Zhang, Kang |
| description | An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive ‘liquid biopsy’ for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (
P
< 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (
P
< 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.
Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients. |
| doi_str_mv | 10.1038/nmat4997 |
| format | Article |
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P
< 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (
P
< 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.
Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.</description><identifier>ISSN: 1476-1122</identifier><identifier>EISSN: 1476-4660</identifier><identifier>DOI: 10.1038/nmat4997</identifier><identifier>PMID: 29035356</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/2210 ; 631/67/1857 ; Aberration ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Biomaterials ; Blood ; Cancer ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - diagnosis ; Carcinoma, Hepatocellular - genetics ; Circulating Tumor DNA - blood ; Circulating Tumor DNA - genetics ; Condensed Matter Physics ; Deoxyribonucleic acid ; Diagnosis ; Diagnostic systems ; DNA ; DNA Methylation ; Female ; Hepatology ; Humans ; Leukocytes ; Liver cancer ; Liver Neoplasms - blood ; Liver Neoplasms - diagnosis ; Liver Neoplasms - genetics ; Male ; Markers ; Materials Science ; Mathematical models ; Medical diagnosis ; Medical prognosis ; Models, Biological ; Nanotechnology ; Optical and Electronic Materials ; Prediction models ; Prognosis ; Tumors</subject><ispartof>Nature materials, 2017-11, Vol.16 (11), p.1155-1161</ispartof><rights>Springer Nature Limited 2017</rights><rights>Copyright Nature Publishing Group Nov 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-fa7758e7952b6cf0a357ebfc8d05604e778a0e8949bed5350a01e55f4112039c3</citedby><cites>FETCH-LOGICAL-c384t-fa7758e7952b6cf0a357ebfc8d05604e778a0e8949bed5350a01e55f4112039c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nmat4997$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nmat4997$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29035356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Rui-hua</creatorcontrib><creatorcontrib>Wei, Wei</creatorcontrib><creatorcontrib>Krawczyk, Michal</creatorcontrib><creatorcontrib>Wang, Wenqiu</creatorcontrib><creatorcontrib>Luo, Huiyan</creatorcontrib><creatorcontrib>Flagg, Ken</creatorcontrib><creatorcontrib>Yi, Shaohua</creatorcontrib><creatorcontrib>Shi, William</creatorcontrib><creatorcontrib>Quan, Qingli</creatorcontrib><creatorcontrib>Li, Kang</creatorcontrib><creatorcontrib>Zheng, Lianghong</creatorcontrib><creatorcontrib>Zhang, Heng</creatorcontrib><creatorcontrib>Caughey, Bennett A.</creatorcontrib><creatorcontrib>Zhao, Qi</creatorcontrib><creatorcontrib>Hou, Jiayi</creatorcontrib><creatorcontrib>Zhang, Runze</creatorcontrib><creatorcontrib>Xu, Yanxin</creatorcontrib><creatorcontrib>Cai, Huimin</creatorcontrib><creatorcontrib>Li, Gen</creatorcontrib><creatorcontrib>Hou, Rui</creatorcontrib><creatorcontrib>Zhong, Zheng</creatorcontrib><creatorcontrib>Lin, Danni</creatorcontrib><creatorcontrib>Fu, Xin</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Duan, Yaou</creatorcontrib><creatorcontrib>Yu, Meixing</creatorcontrib><creatorcontrib>Ying, Binwu</creatorcontrib><creatorcontrib>Zhang, Wengeng</creatorcontrib><creatorcontrib>Wang, Juan</creatorcontrib><creatorcontrib>Zhang, Edward</creatorcontrib><creatorcontrib>Zhang, Charlotte</creatorcontrib><creatorcontrib>Li, Oulan</creatorcontrib><creatorcontrib>Guo, Rongping</creatorcontrib><creatorcontrib>Carter, Hannah</creatorcontrib><creatorcontrib>Zhu, Jian-kang</creatorcontrib><creatorcontrib>Hao, Xiaoke</creatorcontrib><creatorcontrib>Zhang, Kang</creatorcontrib><title>Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma</title><title>Nature materials</title><addtitle>Nature Mater</addtitle><addtitle>Nat Mater</addtitle><description>An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive ‘liquid biopsy’ for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (
P
< 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (
P
< 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.
Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.</description><subject>631/1647/2210</subject><subject>631/67/1857</subject><subject>Aberration</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomaterials</subject><subject>Blood</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - diagnosis</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Circulating Tumor DNA - blood</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Condensed Matter Physics</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - diagnosis</subject><subject>Liver Neoplasms - genetics</subject><subject>Male</subject><subject>Markers</subject><subject>Materials Science</subject><subject>Mathematical models</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Models, Biological</subject><subject>Nanotechnology</subject><subject>Optical and Electronic Materials</subject><subject>Prediction models</subject><subject>Prognosis</subject><subject>Tumors</subject><issn>1476-1122</issn><issn>1476-4660</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkLtOwzAYRi0EoqUg8QTIEgsMATu-JB6rcpUqWGCOHMduUxq72MnQt8dRU0CdfDs6_v4PgEuM7jAi-b1tZEuFyI7AGNOMJ5RzdDzsMU7TETgLYYVQihnjp2CUCkQYYXwMylntVbeWbW0XsO0a13n48DaFjW6X2_7aWdhI_6V9gMZ5WNVyYV2oA5S2ghvvhpMzcKk3snVKr9fR56GSXtXWNfIcnBi5DvpiWCfg8-nxY_aSzN-fX2fTeaJITtvEyCxjuc4ES0uuDJKEZbo0Kq8Q44jqLMsl0rmgotRVDI8kwpoxQ-OAiAhFJuBm542pvjsd2qKpQx9HWu26UGDBMOMEcRLR6wN0FQe3MV1PMU5TkeM_ofIuBK9NsfF1LGNbYFT0vRf73iN6NQi7stHVL7gvOgK3OyDEJ7vQ_t-Ph7IfhsGMbQ</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Xu, Rui-hua</creator><creator>Wei, Wei</creator><creator>Krawczyk, Michal</creator><creator>Wang, Wenqiu</creator><creator>Luo, Huiyan</creator><creator>Flagg, Ken</creator><creator>Yi, 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tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma</title><author>Xu, Rui-hua ; Wei, Wei ; Krawczyk, Michal ; Wang, Wenqiu ; Luo, Huiyan ; Flagg, Ken ; Yi, Shaohua ; Shi, William ; Quan, Qingli ; Li, Kang ; Zheng, Lianghong ; Zhang, Heng ; Caughey, Bennett A. ; Zhao, Qi ; Hou, Jiayi ; Zhang, Runze ; Xu, Yanxin ; Cai, Huimin ; Li, Gen ; Hou, Rui ; Zhong, Zheng ; Lin, Danni ; Fu, Xin ; Zhu, Jie ; Duan, Yaou ; Yu, Meixing ; Ying, Binwu ; Zhang, Wengeng ; Wang, Juan ; Zhang, Edward ; Zhang, Charlotte ; Li, Oulan ; Guo, Rongping ; Carter, Hannah ; Zhu, Jian-kang ; Hao, Xiaoke ; Zhang, Kang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-fa7758e7952b6cf0a357ebfc8d05604e778a0e8949bed5350a01e55f4112039c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/1647/2210</topic><topic>631/67/1857</topic><topic>Aberration</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomaterials</topic><topic>Blood</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - diagnosis</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Circulating Tumor DNA - blood</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Condensed Matter Physics</topic><topic>Deoxyribonucleic acid</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - diagnosis</topic><topic>Liver Neoplasms - genetics</topic><topic>Male</topic><topic>Markers</topic><topic>Materials Science</topic><topic>Mathematical models</topic><topic>Medical diagnosis</topic><topic>Medical prognosis</topic><topic>Models, Biological</topic><topic>Nanotechnology</topic><topic>Optical and Electronic Materials</topic><topic>Prediction models</topic><topic>Prognosis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Rui-hua</creatorcontrib><creatorcontrib>Wei, Wei</creatorcontrib><creatorcontrib>Krawczyk, Michal</creatorcontrib><creatorcontrib>Wang, Wenqiu</creatorcontrib><creatorcontrib>Luo, Huiyan</creatorcontrib><creatorcontrib>Flagg, Ken</creatorcontrib><creatorcontrib>Yi, 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markers for diagnosis and prognosis of hepatocellular carcinoma</atitle><jtitle>Nature materials</jtitle><stitle>Nature Mater</stitle><addtitle>Nat Mater</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>16</volume><issue>11</issue><spage>1155</spage><epage>1161</epage><pages>1155-1161</pages><issn>1476-1122</issn><eissn>1476-4660</eissn><abstract>An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive ‘liquid biopsy’ for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (
P
< 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (
P
< 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.
Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29035356</pmid><doi>10.1038/nmat4997</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1476-1122 |
| ispartof | Nature materials, 2017-11, Vol.16 (11), p.1155-1161 |
| issn | 1476-1122 1476-4660 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals; Nature |
| subjects | 631/1647/2210 631/67/1857 Aberration Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Biomaterials Blood Cancer Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - genetics Circulating Tumor DNA - blood Circulating Tumor DNA - genetics Condensed Matter Physics Deoxyribonucleic acid Diagnosis Diagnostic systems DNA DNA Methylation Female Hepatology Humans Leukocytes Liver cancer Liver Neoplasms - blood Liver Neoplasms - diagnosis Liver Neoplasms - genetics Male Markers Materials Science Mathematical models Medical diagnosis Medical prognosis Models, Biological Nanotechnology Optical and Electronic Materials Prediction models Prognosis Tumors |
| title | Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T08%3A06%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Circulating%20tumour%20DNA%20methylation%20markers%20for%20diagnosis%20and%20prognosis%20of%20hepatocellular%20carcinoma&rft.jtitle=Nature%20materials&rft.au=Xu,%20Rui-hua&rft.date=2017-11-01&rft.volume=16&rft.issue=11&rft.spage=1155&rft.epage=1161&rft.pages=1155-1161&rft.issn=1476-1122&rft.eissn=1476-4660&rft_id=info:doi/10.1038/nmat4997&rft_dat=%3Cproquest_cross%3E1951563063%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1955642981&rft_id=info:pmid/29035356&rfr_iscdi=true |