An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients
An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients
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DOI：
10.1007/s10549-009-0674-9
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发表时间：
2010-10-01
影响因子：
3.8
通讯作者：
Szallasi, Zoltan
中科院分区：
文献类型：
--
作者：
Gyoerffy, Balazs;Lanczky, Andras;Szallasi, Zoltan
在适当功率的乳腺癌队列中验证预后或预测候选基因是最令人感兴趣的。我们的目标是开发一种在线工具来绘制生存图，可用于评估未经治疗和治疗的乳腺癌患者中各种基因的表达水平与临床结果的相关性。使用从 GEO 下载的 1,809 名患者的基因表达数据和生存信息（Affymetrix HGU133A 和 HGU133+2 微阵列）建立背景数据库。中位无复发生存期为 6.43 年，968/1,231 例患者雌激素受体 (ER) 阳性，190/1,369 例淋巴结阳性。经过质量控制和标准化后，仅保留两个 Affymetrix 平台上存在的探针 (n = 22,277)。为了分析特定基因的预后价值，根据该基因的中值（或上/下四分位数）表达将队列分为两组。可以在无复发生存率、总生存率和无远处转移生存率方面比较两组。显示生存曲线，并计算并显示具有 95% 置信区间的风险比和对数秩 P 值。此外，还可以评估三个亚组患者：未经系统治疗的患者、接受内分泌治疗的 ER 阳性患者以及具有代表美国一般临床实践中所见临床特征分布的患者。网址：www.kmplot.com。我们使用这种综合数据分析工具来确认增殖相关基因 TOP2A 和 TOP2B、MKI67、CCND2、CCND3、CCNDE2 以及 CDKN1A 和 TK2 的预后能力。我们还验证了微阵列确定 1,231 名患者雌激素受体状态的能力。该工具对于生物标志物的初步评估非常有价值，特别是对于生物信息资源有限的研究小组而言。
Validating prognostic or predictive candidate genes in appropriately powered breast cancer cohorts are of utmost interest. Our aim was to develop an online tool to draw survival plots, which can be used to assess the relevance of the expression levels of various genes on the clinical outcome both in untreated and treated breast cancer patients. A background database was established using gene expression data and survival information of 1,809 patients downloaded from GEO (Affymetrix HGU133A and HGU133+2 microarrays). The median relapse free survival is 6.43 years, 968/1,231 patients are estrogen-receptor (ER) positive, and 190/1,369 are lymph-node positive. After quality control and normalization only probes present on both Affymetrix platforms were retained (n = 22,277). In order to analyze the prognostic value of a particular gene, the cohorts are divided into two groups according to the median (or upper/lower quartile) expression of the gene. The two groups can be compared in terms of relapse free survival, overall survival, and distant metastasis free survival. A survival curve is displayed, and the hazard ratio with 95% confidence intervals and logrank P value are calculated and displayed. Additionally, three subgroups of patients can be assessed: systematically untreated patients, endocrine-treated ER positive patients, and patients with a distribution of clinical characteristics representative of those seen in general clinical practice in the US. Web address: www.kmplot.com. We used this integrative data analysis tool to confirm the prognostic power of the proliferation-related genes TOP2A and TOP2B, MKI67, CCND2, CCND3, CCNDE2, as well as CDKN1A, and TK2. We also validated the capability of microarrays to determine estrogen receptor status in 1,231 patients. The tool is highly valuable for the preliminary assessment of biomarkers, especially for research groups with limited bioinformatic resources.