Nomogram Integrating Genomics with Clinicopathologic Features Improves Prognosis Prediction for Colorectal Cancer
Nomogram Integrating Genomics with Clinicopathologic Features Improves Prognosis Prediction for Colorectal Cancer
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DOI：
10.1158/1541-7786.mcr-18-0063
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发表时间：
2018-09-01
影响因子：
5.2
通讯作者：
Fu, Zhongxue
中科院分区：
文献类型：
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作者：
Xiong, Yongfu;You, Wenxian;Fu, Zhongxue
由于结直肠癌的表型和基因组异质性，目前的肿瘤分期系统不足以预测结直肠癌患者的预后。将基因表达特征与临床病理因素相结合可能会产生超过当前可用系统的预测准确性。27个使用基因表达数据预测结直肠癌预后的特征被鉴定并使用生物信息学方法重新分析。接下来，将具有相应表达谱的临床注释的结直肠癌样品（n = 1710）合并，以评估其预后价值并建立临床病理基因组列线图，所述表达谱预测患者的癌症复发概率。在所评估的27个特征中，只有2个显示出与预后显著相关，并在汇总队列中提供了合理的预测准确性（HR，2.46; 95%CI，1.183-5.132，P < 0.001; AUC，60.83; HR，2.33; 95%CI，1.218-4.453，P < 0.001; AUC，71.34）。通过将上述特征与预后临床病理学特征相结合，谨慎地构建了临床病理学-基因组列线图。诺模图成功地将结直肠癌患者分为具有显著不同DFS率的三个风险组，并进一步将II期和III期患者分为不同的风险亚组。重要的是，在接受化疗的患者中，诺模图确定那些处于中间状态的患者-（HR，0.98; 95%CI，0.255-0.679，P < 0.001）和高危（HR，0.67; 95%CI，0.469-0.957，P = 0.028）组的反应良好。这些发现提供了证据，表明基因组数据提供了独立和互补的预后信息，并且这些信息的整合可以改善结直肠癌的预后。(C)2018年AACR。
The current tumor staging system is insufficient for predicting the outcomes for patients with colorectal cancer because of its phenotypic and genomic heterogeneity. Integrating gene expression signatures with clinicopathologic factors may yield a predictive accuracy exceeding that of the currently available system. Twenty-seven signatures that used gene expression data to predict colorectal cancer prognosis were identified and re-analyzed using bioinformatic methods. Next, clinically annotated colorectal cancer samples (n = 1710) with the corresponding expression profiles, that predicted a patient's probability of cancer recurrence, were pooled to evaluate their prognostic values and establish a clinicopathologic-genomic nomogram. Only 2 of the 27 signatures evaluated showed a significant association with prognosis and provided a reasonable prediction accuracy in the pooled cohort (HR, 2.46; 95% CI, 1.183-5.132, P < 0.001; AUC, 60.83; HR, 2.33; 95% CI, 1.218-4.453, P < 0.001; AUC, 71.34). By integrating the above signatures with prognostic clinicopathologic features, a clinicopathologic-genomic nomogram was cautiously constructed. The nomogram successfully stratified colorectal cancer patients into three risk groups with remarkably different DFS rates and further stratified stage II and III patients into distinct risk subgroups. Importantly, among patients receiving chemotherapy, the nomogram determined that those in the intermediate-(HR, 0.98; 95% CI, 0.255-0.679, P < 0.001) and high-risk (HR, 0.67; 95% CI, 0.469-0.957, P = 0.028) groups had favorable responses.Implications: These findings offer evidence that genomic data provide independent and complementary prognostic information, and incorporation of this information refines the prognosis of colorectal cancer. (C) 2018 AACR.