Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.26/19005 |
Resumo: | Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab. |
id |
RCAP_9ef170551d5c488d1933774e358265e7 |
---|---|
oai_identifier_str |
oai:comum.rcaap.pt:10400.26/19005 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancerBiomarcadores TumoraisNeoplasias ColorrectaisDNA de NeoplasiasProteínas de MembranaProteínas de NeoplasiasBiomarkers, TumorDNA, NeoplasmColorectal NeoplasmsMembrane ProteinsNeoplasm ProteinsDetection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab.Repositório ComumHerbst, AVdovin, NGacesa, SPhilipp, ANagel, DHoldt, LMOp den Winkel, MHeinemann, VStieber, PGraeven, UReinacher-Schick, AArnold, DRicard, IMansmann, UHegewisch-Becker, SKolligs, F T2017-09-25T20:57:54Z2017-05-012017-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.26/19005engInt J Cancer. 2017 May 1;140(9):2134-2144.10.1002/ijc.30625info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-12-20T14:25:11Zoai:comum.rcaap.pt:10400.26/19005Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:22:45.528777Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
title |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
spellingShingle |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer Herbst, A Biomarcadores Tumorais Neoplasias Colorrectais DNA de Neoplasias Proteínas de Membrana Proteínas de Neoplasias Biomarkers, Tumor DNA, Neoplasm Colorectal Neoplasms Membrane Proteins Neoplasm Proteins |
title_short |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
title_full |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
title_fullStr |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
title_full_unstemmed |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
title_sort |
Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer |
author |
Herbst, A |
author_facet |
Herbst, A Vdovin, N Gacesa, S Philipp, A Nagel, D Holdt, LM Op den Winkel, M Heinemann, V Stieber, P Graeven, U Reinacher-Schick, A Arnold, D Ricard, I Mansmann, U Hegewisch-Becker, S Kolligs, F T |
author_role |
author |
author2 |
Vdovin, N Gacesa, S Philipp, A Nagel, D Holdt, LM Op den Winkel, M Heinemann, V Stieber, P Graeven, U Reinacher-Schick, A Arnold, D Ricard, I Mansmann, U Hegewisch-Becker, S Kolligs, F T |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Comum |
dc.contributor.author.fl_str_mv |
Herbst, A Vdovin, N Gacesa, S Philipp, A Nagel, D Holdt, LM Op den Winkel, M Heinemann, V Stieber, P Graeven, U Reinacher-Schick, A Arnold, D Ricard, I Mansmann, U Hegewisch-Becker, S Kolligs, F T |
dc.subject.por.fl_str_mv |
Biomarcadores Tumorais Neoplasias Colorrectais DNA de Neoplasias Proteínas de Membrana Proteínas de Neoplasias Biomarkers, Tumor DNA, Neoplasm Colorectal Neoplasms Membrane Proteins Neoplasm Proteins |
topic |
Biomarcadores Tumorais Neoplasias Colorrectais DNA de Neoplasias Proteínas de Membrana Proteínas de Neoplasias Biomarkers, Tumor DNA, Neoplasm Colorectal Neoplasms Membrane Proteins Neoplasm Proteins |
description |
Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-09-25T20:57:54Z 2017-05-01 2017-05-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.26/19005 |
url |
http://hdl.handle.net/10400.26/19005 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Int J Cancer. 2017 May 1;140(9):2134-2144. 10.1002/ijc.30625 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799130672834543616 |