A 25-signal proteomic signature and outcome for patients with resected non-small-cell lung cancer
A 25-signal proteomic signature and outcome for patients with resected non-small-cell lung cancer
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DOI：
10.1093/jnci/djk197
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发表时间：
2007-06-06
影响因子：
10.3
通讯作者：
Takahashi, Takashi
中科院分区：
文献类型：
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作者：
Yanagisawa, Kiyoshi;Tomida, Shuta;Takahashi, Takashi
背景非小细胞肺癌（non-small-cell lung cancer，NSCLC）患者中预后不良者与预后良好者不能区分。方法采用基质辅助激光解吸电离质谱（Matrix-assisted laser desorption-ionization mass spectrometry，MALDI-MS）技术分析174例NSCLC肿瘤组织和27例正常肺组织的蛋白质组学特征，并建立NSCLC相关蛋白质组学特征。将冷冻切除的组织标本随机分为训练集（116份NSCLC和20份正常肺标本）和独立的盲法验证集（58份NSCLC和7份正常肺标本）。来自训练集样本的质谱信号与来自具有高复发风险的患者（即，由于复发而在手术治疗5年内死亡的患者）与复发风险低的患者（即，中位随访89个月后无复发症状的存活患者）通过使用Fisher精确检验、Kruskal-Wallis检验和微阵列检验的显著性分析来选择。这些信号用于建立个性化的、加权的基于投票的预后特征。然后在独立数据集中验证签名。通过多变量考克斯回归分析评估生存率。通过离子阱质谱结合高效液相色谱法鉴定对应于单个信号的蛋白质。所有的统计检验都是双侧的。结果从2630个质谱信号的标本在训练队列中，我们得出了一个签名的25个信号，这是与无复发生存和总生存。在验证集中的I期非小细胞肺癌患者中，该特征与总生存期在统计学上显着相关（高风险组患者与低风险组患者的死亡风险比[HR]= 61.1，95%置信区间[CI] = 8.9至419.2，P
Background Among patients with non-small-cell lung cancer (NSCLC), those with poor prognosis cannot be distinguished from those with good prognosis.Methods Matrix-assisted laser desorption-ionization mass spectrometry was used to analyze protein profiles of 174 specimens from NSCLC tumors and 27 specimens from normal lung tissue and to derive a prognosis-associated proteomic signature. Frozen resected tissue specimens were randomly divided into a training set (116 NSCLC and 20 normal lung specimens) and an independent, blinded validation set (58 NSCLC and seven normal lung specimens). Mass spectrometry signals from training set specimens that were differentially associated with specimens from patients with a high risk of recurrence (i.e., who died within 5 years of surgical treatment because of relapse) compared with those from patients with a low risk of recurrence (i.e., alive with no symptoms of relapse after a median follow-up of 89 months) were selected by use of the Fisher's exact test, the Kruskal-Wallis test, and the significance analysis of microarray test. These signals were used to build an individualized, weighted voting-based prognostic signature. The signature was then validated in the independent dataset. Survival was assessed by multivariable Cox regression analysis. Proteins corresponding to individual signals were identified by ion-trap mass spectrometry coupled with high-performance liquid chromatography. All statistical tests were two-sided.Results From 2630 mass spectrometry signals from specimens in the training cohort, we derived a signature of 25 signals that was associated with both relapse-free survival and overall survival. Among stage I NSCLC patients in the validation set, the signature was statistically significantly associated with both overall survival (hazard ratio [HR] of death for patients in the high-risk group compared with those in the low-risk group = 61.1, 95% confidence interval [CI] = 8.9 to 419.2, P