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CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer

DC FieldValueLanguage
dc.contributor.author백순명-
dc.date.accessioned2017-02-24T08:15:45Z-
dc.date.available2017-02-24T08:15:45Z-
dc.date.issued2016-
dc.identifier.issn0028-4793-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/146602-
dc.description.abstractBackground The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).-
dc.description.statementOfResponsibilityopen-
dc.format.extent211~222-
dc.languageEnglish-
dc.publisherMassachusetts Medical Society-
dc.relation.isPartOfNEW ENGLAND JOURNAL OF MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnalysis of Variance-
dc.subject.MESHAntineoplastic Agents/therapeutic use*-
dc.subject.MESHBiomarkers, Tumor/genetics-
dc.subject.MESHBiomarkers, Tumor/metabolism*-
dc.subject.MESHCDX2 Transcription Factor-
dc.subject.MESHChemotherapy, Adjuvant-
dc.subject.MESHColonic Neoplasms/drug therapy-
dc.subject.MESHColonic Neoplasms/genetics*-
dc.subject.MESHColonic Neoplasms/metabolism-
dc.subject.MESHColonic Neoplasms/pathology-
dc.subject.MESHComputational Biology-
dc.subject.MESHDatabases, Genetic-
dc.subject.MESHDisease-Free Survival-
dc.subject.MESHFemale-
dc.subject.MESHGene Expression*-
dc.subject.MESHHomeodomain Proteins/genetics-
dc.subject.MESHHomeodomain Proteins/metabolism*-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHNeoplasm Staging-
dc.subject.MESHOligonucleotide Array Sequence Analysis-
dc.subject.MESHPrognosis-
dc.subject.MESHRNA, Messenger/metabolism-
dc.subject.MESHRetrospective Studies-
dc.titleCDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorPiero Dalerba-
dc.contributor.googleauthorDebashis Sahoo-
dc.contributor.googleauthorSoonmyung Paik-
dc.contributor.googleauthorXiangqian Guo-
dc.contributor.googleauthorGreg Yothers-
dc.contributor.googleauthorNan Song-
dc.contributor.googleauthorNate Wilcox-Fogel-
dc.contributor.googleauthorErna Forgó-
dc.contributor.googleauthorPradeep S. Rajendran-
dc.contributor.googleauthorStephen P. Miranda-
dc.contributor.googleauthorShigeo Hisamori-
dc.contributor.googleauthorJacqueline Hutchison-
dc.contributor.googleauthorTomer Kalisky-
dc.contributor.googleauthorDalong Qian-
dc.contributor.googleauthorNorman Wolmark-
dc.contributor.googleauthorGeorge A. Fisher-
dc.contributor.googleauthorMatt van de Rijn-
dc.contributor.googleauthorMichael F. Clarke-
dc.identifier.doi10.1056/NEJMoa1506597-
dc.contributor.localIdA01823-
dc.relation.journalcodeJ02371-
dc.identifier.eissn1533-4406-
dc.identifier.pmid26789870-
dc.contributor.alternativeNamePaik, Soon Myung-
dc.contributor.affiliatedAuthorPaik, Soon Myung-
dc.citation.volume374-
dc.citation.number3-
dc.citation.startPage211-
dc.citation.endPage222-
dc.identifier.bibliographicCitationNEW ENGLAND JOURNAL OF MEDICINE, Vol.374(3) : 211-222, 2016-
dc.date.modified2017-02-24-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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