DC Field | Value | Language |
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dc.contributor.author | S A Roh | - |
dc.contributor.author | I J Park | - |
dc.contributor.author | Y S Yoon | - |
dc.contributor.author | Y H Kwon | - |
dc.contributor.author | J H Chung | - |
dc.contributor.author | T W Kim | - |
dc.contributor.author | D H Cho | - |
dc.contributor.author | Byung Ho Lim | - |
dc.contributor.author | Seon-Kyu Kim | - |
dc.contributor.author | Seon-Young Kim | - |
dc.contributor.author | Yong Sung Kim | - |
dc.contributor.author | J C Kim | - |
dc.date.accessioned | 2017-04-19T10:29:00Z | - |
dc.date.available | 2017-04-19T10:29:00Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 0171-5216 | - |
dc.identifier.uri | 10.1007/s00432-016-2177-5 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/13487 | - |
dc.description.abstract | Purpose: 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.publisher | Springer | - |
dc.title | Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer | - |
dc.title.alternative | Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer | - |
dc.type | Article | - |
dc.citation.title | Journal of Cancer Research and Clinical Oncology | - |
dc.citation.number | 0 | - |
dc.citation.endPage | 1714 | - |
dc.citation.startPage | 1705 | - |
dc.citation.volume | 142 | - |
dc.contributor.affiliatedAuthor | Byung Ho Lim | - |
dc.contributor.affiliatedAuthor | Seon-Kyu Kim | - |
dc.contributor.affiliatedAuthor | Seon-Young Kim | - |
dc.contributor.affiliatedAuthor | Yong Sung Kim | - |
dc.contributor.alternativeName | 노선애 | - |
dc.contributor.alternativeName | 박인자 | - |
dc.contributor.alternativeName | 윤용식 | - |
dc.contributor.alternativeName | 권이홍 | - |
dc.contributor.alternativeName | 정진화 | - |
dc.contributor.alternativeName | 김태원 | - |
dc.contributor.alternativeName | 조동형 | - |
dc.contributor.alternativeName | 임병호 | - |
dc.contributor.alternativeName | 김선규 | - |
dc.contributor.alternativeName | 김선영 | - |
dc.contributor.alternativeName | 김용성 | - |
dc.contributor.alternativeName | 김진철 | - |
dc.identifier.bibliographicCitation | Journal of Cancer Research and Clinical Oncology, vol. 142, pp. 1705-1714 | - |
dc.identifier.doi | 10.1007/s00432-016-2177-5 | - |
dc.subject.keyword | ANXA11 | - |
dc.subject.keyword | Bevacizumab | - |
dc.subject.keyword | Metastatic colorectal cancer | - |
dc.subject.keyword | PPP1R15A | - |
dc.subject.keyword | Predictive marker | - |
dc.subject.local | ANXA11 | - |
dc.subject.local | Bevacizumab | - |
dc.subject.local | Metastatic colorectal cancer | - |
dc.subject.local | PPP1R15A | - |
dc.subject.local | predictive marker | - |
dc.subject.local | Predictive marker | - |
dc.description.journalClass | Y | - |
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