Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer

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dc.contributor.authorS A Roh-
dc.contributor.authorI J Park-
dc.contributor.authorY S Yoon-
dc.contributor.authorY H Kwon-
dc.contributor.authorJ H Chung-
dc.contributor.authorT W Kim-
dc.contributor.authorD H Cho-
dc.contributor.authorByung Ho Lim-
dc.contributor.authorSeon-Kyu Kim-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorYong Sung Kim-
dc.contributor.authorJ C Kim-
dc.date.accessioned2017-04-19T10:29:00Z-
dc.date.available2017-04-19T10:29:00Z-
dc.date.issued2016-
dc.identifier.issn0171-5216-
dc.identifier.uri10.1007/s00432-016-2177-5ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13487-
dc.description.abstractPurpose: Bevacizumab improves survival in patients with metastatic colorectal cancer (mCRC) under chemotherapy, but few predictive markers have been identified. Methods: To investigate chemosensitive single nucleotide polymorphisms (SNPs) of mCRC, we performed exome sequencing and RNA sequencing in 19 patients. A clinical association analysis was performed with the other 116 patients who had received chemotherapy to bevacizumab regimens. In vivo biodistribution studies and [18F]FDG-PET imaging were performed on mice bearing human colorectal cancer (HCT116 and SW480) xenografts after injection of bevacizumab with 5-FU, leucovorin, and irinotecan (FOLFIRI). Results: PPP1R15Ars557806 showed the most significant association with FRB-driven tumor IR in exome sequencing and the highest correlation (r=0.74) with drug responses in RNA sequencing. Patients homozygous for the reference alleles (GG) of PPP1R15A rs557806 exhibited greater disease control rate and a tendency toward greater objective response rate (ORR) than those with homozygous or heterozygous substitution alleles (GC and CC; P=0.027 and 0.073, respectively). In xenografted mice, HCT116 clones transfected with the G allele at PPP1R15A rs557806 were more sensitive to bevacizumab regimens than those with the C allele. Tumor volume of xenografts with the G allele was significantly lower than that of xenografts with the C allele (P=0.004, day 13). [18F]FDG uptake decreased to 75% in HCT116 xenograft-bearing mice with the G allele, whereas [18F]FDG uptake was 42% in mice xenografts with the C allele (P=0.032). ANXA11 rs1049550, a predictive biomarker of SNP described in our previous study, was validated using the xenograft model. Tumor volume and [18F]FDG uptake analyses showed that tumors in the SW480 xenografts expressing the substitution allele (T) at ANXA11 rs1049550 were more susceptible to FOLFIRI plus bevacizumab-induced suppression than those expressing the reference allele (C) (P=0.001 and 0.026, respectively). Conclusion: ANXA11 rs1049550 and PPP1R15A rs557806 may improve the identification of mCRC patients sensitive to bevacizumab regimens, and further validation is required in large cohorts.-
dc.publisherSpringer-
dc.titleFeasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer-
dc.title.alternativeFeasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer-
dc.typeArticle-
dc.citation.titleJournal of Cancer Research and Clinical Oncology-
dc.citation.number0-
dc.citation.endPage1714-
dc.citation.startPage1705-
dc.citation.volume142-
dc.contributor.affiliatedAuthorByung Ho Lim-
dc.contributor.affiliatedAuthorSeon-Kyu Kim-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName노선애-
dc.contributor.alternativeName박인자-
dc.contributor.alternativeName윤용식-
dc.contributor.alternativeName권이홍-
dc.contributor.alternativeName정진화-
dc.contributor.alternativeName김태원-
dc.contributor.alternativeName조동형-
dc.contributor.alternativeName임병호-
dc.contributor.alternativeName김선규-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName김용성-
dc.contributor.alternativeName김진철-
dc.identifier.bibliographicCitationJournal of Cancer Research and Clinical Oncology, vol. 142, pp. 1705-1714-
dc.identifier.doi10.1007/s00432-016-2177-5-
dc.subject.keywordANXA11-
dc.subject.keywordBevacizumab-
dc.subject.keywordMetastatic colorectal cancer-
dc.subject.keywordPPP1R15A-
dc.subject.keywordPredictive marker-
dc.subject.localANXA11-
dc.subject.localBevacizumab-
dc.subject.localMetastatic colorectal cancer-
dc.subject.localPPP1R15A-
dc.subject.localpredictive marker-
dc.subject.localPredictive marker-
dc.description.journalClassY-
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