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DC Field | Value | Language |
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dc.citation.endPage | 16460 | - |
dc.citation.number | 18 | - |
dc.citation.startPage | 16449 | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 6 | - |
dc.contributor.author | Lee, Yeon-Su | - |
dc.contributor.author | Kim, Bo Hyun | - |
dc.contributor.author | Kim, Byung Chul | - |
dc.contributor.author | Shin, Aesun | - |
dc.contributor.author | Kim, Jin Sook | - |
dc.contributor.author | Hong, Seung-Hyun | - |
dc.contributor.author | Hwang, Jung-Ah | - |
dc.contributor.author | Lee, Jung Ahn | - |
dc.contributor.author | Nam, Seungyoon | - |
dc.contributor.author | Lee, Sung Hoon | - |
dc.contributor.author | Bhak, Jong Hwa | - |
dc.contributor.author | Park, Joong-Won | - |
dc.date.accessioned | 2023-12-22T01:10:34Z | - |
dc.date.available | 2023-12-22T01:10:34Z | - |
dc.date.created | 2015-09-02 | - |
dc.date.issued | 2015-06 | - |
dc.description.abstract | Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of > 96 gigabases/sample was generated at average of similar to 34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.6, no.18, pp.16449 - 16460 | - |
dc.identifier.doi | 10.18632/oncotarget.3758 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.scopusid | 2-s2.0-84937920419 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/16563 | - |
dc.identifier.url | http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3758&pubmed-linkout=1 | - |
dc.identifier.wosid | 000359012000072 | - |
dc.language | 영어 | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.title | SLC15A2 genomic variation is associated with the extraordinary response of sorafenib treatment: whole-genome analysis in patients with hepatocellular carcinoma | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Oncology; Cell Biology | - |
dc.relation.journalResearchArea | Oncology; Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | sorafenib | - |
dc.subject.keywordAuthor | whole-genome sequencing | - |
dc.subject.keywordAuthor | genome variations | - |
dc.subject.keywordAuthor | hepatocellular carcinoma | - |
dc.subject.keywordAuthor | extraordinary response | - |
dc.subject.keywordPlus | FLAVIN-CONTAINING MONOOXYGENASE-3 | - |
dc.subject.keywordPlus | GENETIC-VARIANTS | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | POLYMORPHISMS | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | TRANSPORT | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | PEPT2 | - |
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