Gene expression profiles and molecular markers to predict recurrence of dukes' B colon cancer
Gene expression profiles and molecular markers to predict recurrence of dukes' B colon cancer
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DOI：
10.1200/jco.2004.08.186
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发表时间：
2004-05-01
影响因子：
45.3
通讯作者：
Atkins, D
中科院分区：
文献类型：
--
作者：
Wang, YX;Jatkoe, T;Atkins, D
目的Dukes' B结肠癌患者的5年生存率约为75%。在该组中识别高复发风险的患者将允许更好的分期和更明智地使用辅助化疗。在这项研究中，我们使用DNA芯片技术，系统地确定新的预后标志物的肿瘤复发在杜克斯B patient.Patients和方法使用Affytelium U133 a基因芯片含有约22,000个转录本（Affytelium，圣克拉拉，CA），RNA样本来自74例杜克斯B结肠癌进行了分析。31例患者在不到3年的时间内发生肿瘤复发，而43例患者在手术后3年以上保持无病状态。两种监督类预测方法被用来确定基因标记，可以最好地区分患者谁会经历复发和患者谁会保持无病。多变量考克斯模型预测recursion.Results基因表达谱确定了一个23个基因的签名，预测复发的公爵B患者。该签名在36名独立患者中得到验证。整体性能准确率为78%。18例复发患者中有13例和18例无病患者中有15例被正确预测，比值比为13（95%CI，2.6至65; P = 0.003）。Log-rank检验显示预测复发和无病患者的无病时间差异有统计学意义（P =.0001）。结论这些标志物的临床价值是预测复发风险高（13倍风险）的患者可以提前接受辅助治疗，类似于Dukes' C患者。我们的数据突出了预后分析的可行性，可以集中更密集的治疗局限性结肠癌。
Purpose The 5-year survival rate of patients with Dukes' B colon cancer is approximately 75%. Identification of the patients at high risk of recurrence in this group would allow better staging and more informed use of adjuvant chemotherapy. In this study, we used DNA chip technology to systematically identify new prognostic markers for tumor relapse in Dukes' B patients.Patients and Methods Using Affymetrix U133a GeneChip containing approximately 22,000 transcripts (Affymetrix, Santa Clara, CA), RNA samples from 74 patients with Dukes' B colon cancer were analyzed. Thirty-one patients developed tumor relapse in less than 3 years, whereas 43 patients remained disease-free for more than 3 years after surgery. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. A multivariate Cox model was built to predict recurrence.Results Gene expression profiling identified a 23-gene signature that predicts recurrence in Dukes' B patients. This signature was validated in 36 independent patients. The overall performance accuracy was 78%. Thirteen of 18 relapse patients and 15 of 18 disease-free patients were predicted correctly, giving an odds ratio of 13 (95% Cl, 2.6 to 65; P =.003). The log-rank test indicated a significant difference in disease-free time between the predicted relapse and disease-free patients (P =.0001).Conclusion The clinical value of these markers is that the patients at a high predicted risk of relapse (13-fold risk) could be upstaged to receive adjuvant therapy, similar to Dukes' C patients. Our data highlight the feasibility of a prognostic assay that could focus more intensive treatment for localized colon cancer.