Gene-expression pro-files to predict distant metastasis of lymph-node-negative primary breast cancer
Gene-expression pro-files to predict distant metastasis of lymph-node-negative primary breast cancer
复制标题
DOI：
10.1016/s0140-6736(05)17947-1
复制
发表时间：
2005-02-19
期刊：
影响因子：
168.9
通讯作者：
Foekens, JA
中科院分区：
文献类型：
--
作者：
Wang, YX;Klijn, JGM;Foekens, JA
基因表达的全基因组测量可以识别基因活性的模式，对肿瘤进行细分，并可能提供比目前淋巴结阴性乳腺癌患者个体风险评估更好的方法。22000个转录本的表达，这些转录本来自286个未接受辅助系统治疗的淋巴结阴性患者的冷冻肿瘤样品的总RNA。我们鉴定了76个基因标记，其由雌激素受体（ER）阳性患者的60个基因和ER阴性患者的16个基因组成。在随后的171例淋巴结阴性患者的独立检测中，该特征显示出93%的灵敏度和48%的特异性。即使在多变量分析中校正了传统的预后因素（5.55 [2.46-12.5]），基因谱在识别5年内发生远处转移的患者方面也具有高度的信息性（风险比5.67 [95% CI 2.59-12.4]）。在84名绝经前患者的亚组中，76个基因的表达也是一个强有力的转移预后因素（9.60 [2.28-40.5]），87例绝经后患者（4.04 [1.57-10.4]）和79例肿瘤为10-20 mm的患者（14.1 [3.34-59.2]），一组患者的预后预测是特别困难的。解释所确定的签名提供了一个强大的工具，确定远处复发的高风险患者。在独立确认后，识别具有良好预后的患者的能力可以使临床医生避免辅助全身治疗或选择侵略性较小的治疗方案。
Background Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer.Methods We analysed, with Affymetrix Human U133a GeneChips, the expression of 22 000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment.Findings In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult.Interpretation The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.