Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation
DC Field | Value | Language |
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dc.contributor.author | Kim, Ji Hoon | - |
dc.contributor.author | Sohn, Bo Hwa | - |
dc.contributor.author | Lee, Hyun-Sung | - |
dc.contributor.author | Kim, Sang-Bae | - |
dc.contributor.author | Yoo, Jeong Eun | - |
dc.contributor.author | Park, Yun-Yong | - |
dc.contributor.author | Jeong, Woojin | - |
dc.contributor.author | Lee, Sung Sook | - |
dc.contributor.author | Park, Eun Sung | - |
dc.contributor.author | Kaseb, Ahmed | - |
dc.contributor.author | Kim, Baek Hui | - |
dc.contributor.author | Kim, Wan Bae | - |
dc.contributor.author | Yeon, Jong Eun | - |
dc.contributor.author | Byun, Kwan Soo | - |
dc.contributor.author | Chu, In-Sun | - |
dc.contributor.author | Kim, Sung Soo | - |
dc.contributor.author | Wang, Xin Wei | - |
dc.contributor.author | Thorgeirsson, Snorri S. | - |
dc.contributor.author | Luk, John M. | - |
dc.contributor.author | Kang, Koo Jeong | - |
dc.contributor.author | Heo, Jeonghoon | - |
dc.contributor.author | Park, Young Nyun | - |
dc.contributor.author | Lee, Ju-Seog | - |
dc.date.accessioned | 2021-09-05T02:30:28Z | - |
dc.date.available | 2021-09-05T02:30:28Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-12 | - |
dc.identifier.issn | 1549-1277 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/96631 | - |
dc.description.abstract | Background: Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. Methods and Findings: Systematic analysis of gene expression data fromhuman liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (< 1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. Conclusions: Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | INTRAHEPATIC RECURRENCE | - |
dc.subject | RISK-FACTORS | - |
dc.subject | THERAPEUTIC TARGET | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | TUMOR-GROWTH | - |
dc.subject | CANCER | - |
dc.subject | PROGNOSIS | - |
dc.subject | HEPATITIS | - |
dc.subject | RESECTION | - |
dc.title | Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Ji Hoon | - |
dc.contributor.affiliatedAuthor | Kim, Baek Hui | - |
dc.contributor.affiliatedAuthor | Kim, Wan Bae | - |
dc.contributor.affiliatedAuthor | Yeon, Jong Eun | - |
dc.contributor.affiliatedAuthor | Byun, Kwan Soo | - |
dc.identifier.doi | 10.1371/journal.pmed.1001770 | - |
dc.identifier.wosid | 000347002300008 | - |
dc.identifier.bibliographicCitation | PLOS MEDICINE, v.11, no.12 | - |
dc.relation.isPartOf | PLOS MEDICINE | - |
dc.citation.title | PLOS MEDICINE | - |
dc.citation.volume | 11 | - |
dc.citation.number | 12 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | General & Internal Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, General & Internal | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | INTRAHEPATIC RECURRENCE | - |
dc.subject.keywordPlus | RISK-FACTORS | - |
dc.subject.keywordPlus | THERAPEUTIC TARGET | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | PROGNOSIS | - |
dc.subject.keywordPlus | HEPATITIS | - |
dc.subject.keywordPlus | RESECTION | - |
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