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Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer

2017-05-01Journal article Open access
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dc.contributor.authorHerbst, A
dc.contributor.authorVdovin, N
dc.contributor.authorGacesa, S
dc.contributor.authorPhilipp, A
dc.contributor.authorNagel, D
dc.contributor.authorHoldt, LM
dc.contributor.authorOp den Winkel, M
dc.contributor.authorHeinemann, V
dc.contributor.authorStieber, P
dc.contributor.authorGraeven, U
dc.contributor.authorReinacher-Schick, A
dc.contributor.authorArnold, D
dc.contributor.authorRicard, I
dc.contributor.authorMansmann, U
dc.contributor.authorHegewisch-Becker, S
dc.contributor.authorKolligs, F T
dc.date.accessioned2017-09-25T20:57:54Z
dc.date.available2017-09-25T20:57:54Z
dc.date.issued2017-05-01
dc.description.abstractDetection 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Cancer. 2017 May 1;140(9):2134-2144.pt_PT
dc.identifier.doi10.1002/ijc.30625pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.26/19005
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectBiomarcadores Tumoraispt_PT
dc.subjectNeoplasias Colorrectaispt_PT
dc.subjectDNA de Neoplasiaspt_PT
dc.subjectProteínas de Membranapt_PT
dc.subjectProteínas de Neoplasiaspt_PT
dc.subjectBiomarkers, Tumorpt_PT
dc.subjectDNA, Neoplasmpt_PT
dc.subjectColorectal Neoplasmspt_PT
dc.subjectMembrane Proteinspt_PT
dc.subjectNeoplasm Proteinspt_PT
dc.titleMethylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2144pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage2134-2144pt_PT
oaire.citation.volume140pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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