Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma.
Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma.
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DOI：
10.1053/j.gastro.2010.11.034
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发表时间：
2011-03
期刊：
影响因子：
29.4
通讯作者：
Thorgeirsson SS
中科院分区：
文献类型：
--
作者：
Woo HG;Wang XW;Budhu A;Kim YH;Kwon SM;Tang ZY;Sun Z;Harris CC;Thorgeirsson SS
肿瘤抑制基因TP 53的突变与许多癌症的预后相关。然而，TP 53突变位点对肝细胞癌（HCC）患者的预后价值尚不清楚，因为其地理和病因背景的异质性。采用直接测序法对409例原发性肝癌患者（中国人336例，白种人73例）进行TP 53基因突变检测。在中国HCC患者中共发现125个TP 53突变（37.2%）。与野生型TP 53患者相比，TP 53突变的HCC患者的总生存时间较短（风险比[HR]，1.86; 95%置信区间[CI]，1.37-2.52; P<0.001）。热点突变R249 S和V157 F在单变量分析（HR，2.11; 95%CI，1.51-2.94; P<0.001）和多变量分析（HR，1.79; 95%CI，1.29-2.51; P<0.001）中与较差的预后显著相关。基因表达分析揭示了TP 53突变的肿瘤中存在干细胞样特征。这些发现在具有TP 53突变的乳腺和肺肿瘤样品中得到验证。TP 53突变，特别是热点突变R249 S和V157 F，与HCC患者的不良预后相关。TP 53基因突变的肿瘤具有干细胞样基因表达特征，可能与肿瘤的侵袭行为有关。
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 etiological backgrounds. TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n=336) and Caucasian (n=73) patients, using direct sequencing method. 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<0.001). The hotspot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI, 1.51–2.94; P<0.001) and multivariate analyses (HR, 1.79; 95% CI, 1.29–2.51; P<0.001). 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. TP53 mutations, particularly the hotspot 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.
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影响因子：
13.5
作者：
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