Molecular staging for survival prediction of colorectal cancer patients
Molecular staging for survival prediction of colorectal cancer patients
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DOI：
10.1200/jco.2005.00.695
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发表时间：
2005-05-20
影响因子：
45.3
通讯作者：
Yeatman, TJ
中科院分区：
文献类型：
--
作者：
Eschrich, S;Yang, I;Yeatman, TJ
目的Dukes分期是预测结直肠癌预后的金标准；然而，对中期病例的准确分类是有问题的。我们假设分子指纹图谱可以提供更准确的分期，并可能有助于指导辅助治疗。方法采用32000 cDNA芯片对78例人结肠癌标本进行评价，并将结果与生存率进行相关性分析。产生分子分类器来预测结果。结果基于43个核心基因的分子分期预测78例患者36个月总生存期的准确率为90%（敏感性93%，特异性84%）。该结果明显优于Dukes分期（P = 03878），以生存时间区分患者有显著性差异（P < 0.001， log-rank检验），与chance有显著性差异（P < 0.001, 1000个排列）。此外，分类器能够在来自丹麦的独立测试集中区分生存差异。分子分期比传统的临床分期更准确地确定患者的预后（以36个月的生存期为代表），特别是对于Dukes中级B期和C期患者。分类器基于43个核心基因，包括骨桥蛋白和神经调节蛋白，这些基因对本病具有生物学意义。结论这些数据支持进一步评估分子分期以区分预后良好和预后不良的患者，具有指导辅助治疗的潜力。(c) 2005年由美国临床肿瘤学会出版。
Purpose The Dukes' staging system is the gold standard for predicting colorectal cancer prognosis; however, accurate classification of intermediate-stage cases is problematic. We hypothesized that molecular fingerprints could provide more accurate staging and potentially assist in directing adjuvant therapy.Methods A 32,000 cDNA microarray was used to evaluate 78 human colon cancer specimens, and these results were correlated with survival. Molecular classifiers were produced to predict outcome.Results Molecular staging, based on 43 core genes, was 90% accurate (93% sensitivity, 84% specificity) in predicting 36-month overall survival in 78 patients. This result was significantly better than Dukes' staging (P = 03878), discriminated patients into significantly different groups by survival time (P < .001, log-rank test), and was significantly different from chance (P < .001, 1,000 permutations). Furthermore, the classifier was able to discriminate a survival difference in an independent test set from Denmark. Molecular staging identifies patient prognosis (as represented by 36-month survival) more accurately than the traditional clinical staging, particularly for intermediate Dukes' stage B and C patients. The classifier was based on a core set of 43 genes, including osteopontin and neuregulin, which have biologic significance for this disease.Conclusion These data support further evaluation of molecular staging to discriminate good from poor prognosis -patients, with the potential to direct adjuvant therapy. (c) 2005 by American Society of Clinical Oncology.