427 279

Cited 71 times in

Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma

Authors
Woo, HG; Wang, XW; Budhu, A; Kim, YH; Kwon, SM; Tang, ZY; Sun, Z; Harris, CC; Thorgeirsson, SS
Citation
Gastroenterology, 140(3):1063-1070, 2011
Journal Title
Gastroenterology
ISSN
0016-50851528-0012
Abstract
BACKGROUND & AIMS: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds.



METHODS: TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method.



RESULTS: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37-2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations.



CONCLUSIONS: TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation.
MeSH terms
Asian Continental Ancestry Group/geneticsBreast Neoplasms/geneticsCarcinoma, Hepatocellular/ethnology/*genetics/mortality/pathologyDNA Mutational AnalysisEuropean Continental Ancestry Group/geneticsExonsFemaleGene Expression Profiling*Gene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLiver Neoplasms/ethnology/*genetics/mortality/pathologyLung Neoplasms/geneticsMaleMiddle Aged*MutationNeoplastic Stem Cells/*pathologyPrognosisProportional Hazards ModelsReproducibility of ResultsRisk AssessmentRisk FactorsSurvival RateTime FactorsTumor Suppressor Protein p53/*genetics
DOI
10.1053/j.gastro.2010.11.034
PMID
21094160
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
우, 현구
Full Text Link
Files in This Item:
1063-1070.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse