Gene expression profiles accurately predict outcome following liver resection in patients with metastatic colorectal cancer.

Gene expression profiles accurately predict outcome following liver resection in patients with metastatic colorectal cancer.
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转移性结直肠癌患者的肝切除后,基因表达谱准确地预测结果。

DOI:
10.1371/journal.pone.0081680
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
D'Angelica M
D'Angelica M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ito H;Mo Q;Qin LX;Viale A;Maithel SK;Maker AV;Shia J;Kingham P;Allen P;DeMatteo RP;Fong Y;Jarnagin WR;D'Angelica M

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本研究的目的是建立一个基于基因特征的结直肠癌肝转移完全切除患者(MCRC)的分子预后模型。使用Illumina HumanHT-12基因芯片,分析了来自96名接受R 0肝切除术的患者的肝转移瘤的RNA样本。患者被随机分配到训练组(n = 60)和测试组(n = 36)。    通过Cox回归确定与疾病特异性生存期(DSS)和肝脏无复发生存期(LRFS)相关的基因,并使用监督主成分方法在训练集上选择构建分子风险评分(MRS)。然后在独立测试集中评价MRS。分别选择19个和115个基因构建DSS和LRFS的MRS。在测试集中验证了每种MRS;高MRS和低MRS患者的3年DSS/LRFS率分别为42/32%和79/80%(DSS p =0.007,LRFS p =0.046)。   在控制先前验证的临床风险评分(CRS)的多变量模型中,MRS仍然是DSS(p = 0.001)和LRFS(p = 0.03)的显著预测因子。    当CRS和MRS相结合时,患者的区分度更好,低风险组的3年DSS/LRFS率分别为90/89%(两种风险评分均较低),而高风险组为42/26%(两种风险评分均较高)(DSS/LRFS p =0.002/0.004)。 基于基因表达谱的MRS具有较高的预后价值,且与CRS无关。这一发现为更好地对肝脏MCRC患者进行风险分层提供了潜在策略。
The aim of this study was to build a molecular prognostic model based on gene signatures for patients with completely resected hepatic metastases from colorectal cancer (MCRC). Using the Illumina HumanHT-12 gene chip, RNA samples from the liver metastases of 96 patients who underwent R0 liver resection were analyzed. Patients were randomly assigned to a training (n = 60) and test (n = 36) set. The genes associated with disease-specific survival (DSS) and liver-recurrence-free survival (LRFS) were identified by Cox-regression and selected to construct a molecular risk score (MRS) using the supervised principle component method on the training set. The MRS was then evaluated in the independent test set. Nineteen and 115 genes were selected to construct the MRS for DSS and LRFS, respectively. Each MRS was validated in the test set; 3-year DSS/LRFS rates were 42/32% and 79/80% for patients with high and low MRS, respectively (p = 0.007 for DSS and p = 0.046 for LRFS). In a multivariate model controlling for a previously validated clinical risk score (CRS), the MRS remained a significant predictor of DSS (p = 0.001) and LRFS (p = 0.03). When CRS and MRS were combined, the patients were discriminated better with 3-year DSS/LRFS rates of 90/89% in the low risk group (both risk scores low) vs 42/26% in the high risk group (both risk scores high), respectively (p = 0.002/0.004 for DSS/LRFS). MRS based on gene expression profiling has high prognostic value and is independent of CRS. This finding provides a potential strategy for better risk-stratification of patients with liver MCRC.
DOI: 10.1097/00000658-199909000-00004
发表时间: 1999-09-01
期刊: ANNALS OF SURGERY
影响因子: 9
作者:
Fong, Y;Fortner, J;Blumgart, LH
通讯作者: Blumgart, LH
DOI: 10.1097/00000658-199804000-00019
发表时间: 1998-04-01
期刊: ANNALS OF SURGERY
影响因子: 9
作者:
Cady, B;Jenkins, RL;Linehan, DC
通讯作者: Linehan, DC
DOI: 10.1056/nejm199912303412702
发表时间: 1999-12-30
影响因子: 158.5
作者:
Kemeny, N;Huang, Y;Fong, YM
通讯作者: Fong, YM
DOI: 10.1056/nejmoa0804525
发表时间: 2008-11-06
期刊: The New England journal of medicine
影响因子: --
作者:
Hoshida Y;Villanueva A;Kobayashi M;Peix J;Chiang DY;Camargo A;Gupta S;Moore J;Wrobel MJ;Lerner J;Reich M;Chan JA;Glickman JN;Ikeda K;Hashimoto M;Watanabe G;Daidone MG;Roayaie S;Schwartz M;Thung S;Salvesen HB;Gabriel S;Mazzaferro V;Bruix J;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者: Golub TR
DOI: 10.1038/nm733
发表时间: 2002-08-01
期刊: NATURE MEDICINE
影响因子: 82.9
作者:
Beer, DG;Kardia, SLR;Hanash, S
通讯作者: Hanash, S