Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer
Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to eva...
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| Veröffentlicht in: | Cell death & disease 2020-05, Vol.11 (5), p.346-346, Article 346 |
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| creator | Yang, Jian Gong, Yuhua Lam, Vincent K. Shi, Yan Guan, Yanfang Zhang, Yanyan Ji, Liyan Chen, Yongsheng Zhao, Yongliang Qian, Feng Chen, Jun Li, Pingang Zhang, Fan Wang, Jiayin Zhang, Xuanping Yang, Ling Kopetz, Scott Futreal, P. Andrew Zhang, Jianjun Yi, Xin Xia, Xuefeng Yu, Peiwu |
| description | Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (
p
= 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29,
p
|
| doi_str_mv | 10.1038/s41419-020-2531-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7214415</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2401810149</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-b4f7b8e84f270bf38596f26adce453719c7c78465be5bc7e802b9a00c3ff7b23</originalsourceid><addsrcrecordid>eNp1kUtP3TAQha2qVUHAD2BTWeqmmxQ_E2dTCfEoSIhu2FuOM7k1SuzbcVKp_Po6vUApUr3xY75z7PEh5Jizz5xJc5IVV7ytmGCV0JJXD2_IvmCKV8qY9u2L9R45yvmelSElE7p-T_akkK1sjNwnyznAlmb4sUD0IW5oGqgP6JfRzet2XqaE9Pz2lPYwg58zndIIaxkpQg794kbahwwuA3Wxp1uEPqwcFgqxuAINkW5cnjF46l05wEPybnBjhqPH-YDcXV7cnV1VN9--Xp-d3lRey3quOjU0nQGjBtGwbpBGt_Ugatd7UFo2vPWNb4yqdQe68w0YJrrWMeblUIRCHpAvO9vt0k1QVHFGN9othsnhL5tcsP9WYvhuN-mnbQRXiuti8OnRAFP5oTzbKWQP4-gipCVboRg3nHHVFvTjK_Q-LRhLd38oppQ2qyHfUR5TzgjD82M4s2usdherLbHaNVb7UDQfXnbxrHgKsQBiB-RSihvAv1f_3_U3EFawSQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2401044585</pqid></control><display><type>article</type><title>Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Yang, Jian ; Gong, Yuhua ; Lam, Vincent K. ; Shi, Yan ; Guan, Yanfang ; Zhang, Yanyan ; Ji, Liyan ; Chen, Yongsheng ; Zhao, Yongliang ; Qian, Feng ; Chen, Jun ; Li, Pingang ; Zhang, Fan ; Wang, Jiayin ; Zhang, Xuanping ; Yang, Ling ; Kopetz, Scott ; Futreal, P. Andrew ; Zhang, Jianjun ; Yi, Xin ; Xia, Xuefeng ; Yu, Peiwu</creator><creatorcontrib>Yang, Jian ; Gong, Yuhua ; Lam, Vincent K. ; Shi, Yan ; Guan, Yanfang ; Zhang, Yanyan ; Ji, Liyan ; Chen, Yongsheng ; Zhao, Yongliang ; Qian, Feng ; Chen, Jun ; Li, Pingang ; Zhang, Fan ; Wang, Jiayin ; Zhang, Xuanping ; Yang, Ling ; Kopetz, Scott ; Futreal, P. Andrew ; Zhang, Jianjun ; Yi, Xin ; Xia, Xuefeng ; Yu, Peiwu</creatorcontrib><description>Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (
p
= 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29,
p
< 0.0001 and HR = 7.664, 95% CI, 2.916–21.06,
p
= 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-020-2531-z</identifier><identifier>PMID: 32393783</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 631/67/1504/1829 ; 692/53/2423 ; Adult ; Aged ; Antibodies ; Biochemistry ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Circulating Tumor DNA - blood ; Circulating Tumor DNA - genetics ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; DNA sequencing ; Early Detection of Cancer ; Female ; Gastrectomy ; Gastric cancer ; Health risk assessment ; High-Throughput Nucleotide Sequencing ; Humans ; Immunology ; Life Sciences ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplasm, Residual ; Patients ; Predictive Value of Tests ; Prospective Studies ; Risk Assessment ; Risk Factors ; Stomach Neoplasms - blood ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach Neoplasms - surgery ; Survival ; Time Factors</subject><ispartof>Cell death & disease, 2020-05, Vol.11 (5), p.346-346, Article 346</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-b4f7b8e84f270bf38596f26adce453719c7c78465be5bc7e802b9a00c3ff7b23</citedby><cites>FETCH-LOGICAL-c536t-b4f7b8e84f270bf38596f26adce453719c7c78465be5bc7e802b9a00c3ff7b23</cites><orcidid>0000-0001-9647-3416 ; 0000-0001-9717-0142</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214415/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214415/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32393783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Jian</creatorcontrib><creatorcontrib>Gong, Yuhua</creatorcontrib><creatorcontrib>Lam, Vincent K.</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Guan, Yanfang</creatorcontrib><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Ji, Liyan</creatorcontrib><creatorcontrib>Chen, Yongsheng</creatorcontrib><creatorcontrib>Zhao, Yongliang</creatorcontrib><creatorcontrib>Qian, Feng</creatorcontrib><creatorcontrib>Chen, Jun</creatorcontrib><creatorcontrib>Li, Pingang</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Wang, Jiayin</creatorcontrib><creatorcontrib>Zhang, Xuanping</creatorcontrib><creatorcontrib>Yang, Ling</creatorcontrib><creatorcontrib>Kopetz, Scott</creatorcontrib><creatorcontrib>Futreal, P. Andrew</creatorcontrib><creatorcontrib>Zhang, Jianjun</creatorcontrib><creatorcontrib>Yi, Xin</creatorcontrib><creatorcontrib>Xia, Xuefeng</creatorcontrib><creatorcontrib>Yu, Peiwu</creatorcontrib><title>Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (
p
= 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29,
p
< 0.0001 and HR = 7.664, 95% CI, 2.916–21.06,
p
= 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.</description><subject>45/23</subject><subject>631/67/1504/1829</subject><subject>692/53/2423</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Circulating Tumor DNA - blood</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Early Detection of Cancer</subject><subject>Female</subject><subject>Gastrectomy</subject><subject>Gastric cancer</subject><subject>Health risk assessment</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Neoplasm Staging</subject><subject>Neoplasm, Residual</subject><subject>Patients</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Stomach Neoplasms - blood</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - surgery</subject><subject>Survival</subject><subject>Time Factors</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtP3TAQha2qVUHAD2BTWeqmmxQ_E2dTCfEoSIhu2FuOM7k1SuzbcVKp_Po6vUApUr3xY75z7PEh5Jizz5xJc5IVV7ytmGCV0JJXD2_IvmCKV8qY9u2L9R45yvmelSElE7p-T_akkK1sjNwnyznAlmb4sUD0IW5oGqgP6JfRzet2XqaE9Pz2lPYwg58zndIIaxkpQg794kbahwwuA3Wxp1uEPqwcFgqxuAINkW5cnjF46l05wEPybnBjhqPH-YDcXV7cnV1VN9--Xp-d3lRey3quOjU0nQGjBtGwbpBGt_Ugatd7UFo2vPWNb4yqdQe68w0YJrrWMeblUIRCHpAvO9vt0k1QVHFGN9othsnhL5tcsP9WYvhuN-mnbQRXiuti8OnRAFP5oTzbKWQP4-gipCVboRg3nHHVFvTjK_Q-LRhLd38oppQ2qyHfUR5TzgjD82M4s2usdherLbHaNVb7UDQfXnbxrHgKsQBiB-RSihvAv1f_3_U3EFawSQ</recordid><startdate>20200511</startdate><enddate>20200511</enddate><creator>Yang, Jian</creator><creator>Gong, Yuhua</creator><creator>Lam, Vincent K.</creator><creator>Shi, Yan</creator><creator>Guan, Yanfang</creator><creator>Zhang, Yanyan</creator><creator>Ji, Liyan</creator><creator>Chen, Yongsheng</creator><creator>Zhao, Yongliang</creator><creator>Qian, Feng</creator><creator>Chen, Jun</creator><creator>Li, Pingang</creator><creator>Zhang, Fan</creator><creator>Wang, Jiayin</creator><creator>Zhang, Xuanping</creator><creator>Yang, Ling</creator><creator>Kopetz, Scott</creator><creator>Futreal, P. 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Andrew</au><au>Zhang, Jianjun</au><au>Yi, Xin</au><au>Xia, Xuefeng</au><au>Yu, Peiwu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2020-05-11</date><risdate>2020</risdate><volume>11</volume><issue>5</issue><spage>346</spage><epage>346</epage><pages>346-346</pages><artnum>346</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (
p
= 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29,
p
< 0.0001 and HR = 7.664, 95% CI, 2.916–21.06,
p
= 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32393783</pmid><doi>10.1038/s41419-020-2531-z</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-9647-3416</orcidid><orcidid>https://orcid.org/0000-0001-9717-0142</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2020-05, Vol.11 (5), p.346-346, Article 346 |
| issn | 2041-4889 2041-4889 |
| language | eng |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | 45/23 631/67/1504/1829 692/53/2423 Adult Aged Antibodies Biochemistry Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Biomedical and Life Sciences Cell Biology Cell Culture Circulating Tumor DNA - blood Circulating Tumor DNA - genetics Deoxyribonucleic acid Disease-Free Survival DNA DNA sequencing Early Detection of Cancer Female Gastrectomy Gastric cancer Health risk assessment High-Throughput Nucleotide Sequencing Humans Immunology Life Sciences Male Middle Aged Neoplasm Recurrence, Local Neoplasm Staging Neoplasm, Residual Patients Predictive Value of Tests Prospective Studies Risk Assessment Risk Factors Stomach Neoplasms - blood Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach Neoplasms - surgery Survival Time Factors |
| title | Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T14%3A30%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Deep%20sequencing%20of%20circulating%20tumor%20DNA%20detects%20molecular%20residual%20disease%20and%20predicts%20recurrence%20in%20gastric%20cancer&rft.jtitle=Cell%20death%20&%20disease&rft.au=Yang,%20Jian&rft.date=2020-05-11&rft.volume=11&rft.issue=5&rft.spage=346&rft.epage=346&rft.pages=346-346&rft.artnum=346&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-020-2531-z&rft_dat=%3Cproquest_pubme%3E2401810149%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2401044585&rft_id=info:pmid/32393783&rfr_iscdi=true |