A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.
A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.
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预测切除非鳞状非小细胞肺癌生存率的实用分子测定：开发和国际验证研究
DOI：
10.1016/s0140-6736(11)61941-7
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发表时间：
2012-03-03
期刊：
影响因子：
168.9
通讯作者：
Jablons, David M.
中科院分区：
文献类型：
--
作者：
Kratz, Johannes R.;He, Jianxing;Van den Eeden, Stephen K.;Zhu, Zhi-Hua;Gao, Wen;Pham, Patrick T.;Mulvihill, Michael S.;Ziaei, Fatemeh;Zhang, Huanrong;Su, Bo;Zhi, Xiuyi;Quesenberry, Charles P.;Habel, Laurel A.;Deng, Qiuhua;Wang, Zongfei;Zhou, Jiangfen;Li, Huiling;Huang, Mei-Chun;Yeh, Che-Chung;Segal, Mark R.;Ray, M. Roshni;Jones, Kirk D.;Raz, Dan J.;Xu, Zhidong;Jahan, Thierry M.;Berryman, David;He, Biao;Mann, Michael J.;Jablons, David M.
早期非小细胞肺癌（NSCLC）的频繁复发通常归因于完全切除时未检测到的转移性疾病。这类患者的管理取决于预后分期，以确定最有可能患有隐匿性疾病的个体。我们的目的是开发和验证一种实用、可靠的检测方法，与传统分期相比，该方法可改善风险分层。在弗朗西斯科加州大学切除的361例非鳞状NSCLC患者队列中，开发了一种14基因表达检测方法，该方法使用定量PCR，在福尔马林固定的石蜡包埋组织样本上运行，并区分具有异质性统计学差异的患者。然后，由Kaiser Permanente研究部在一个设盲队列（由433例在Kaiser Permanente北方加州医院切除的I期非鳞状NSCLC患者组成）和一个队列（由1006例在中国临床试验联盟（CCTC）的几家领先癌症中心切除的I-III期非鳞状NSCLC患者组成）中对该检测方法进行了独立验证。Kaiser验证队列的Kaplan-Meier分析显示，低风险患者的5年总生存率为71.4%（95%CI 60.5 - 80.0），中风险患者为58.3%（48.9 - 66.6），高风险患者为49.2%（42.2 - 55.8）（ptrend= 0.0003）。CCT队列的类似分析表明，低风险患者的5年总生存率为74.1%（66.0 - 80.6），中风险患者为57.4%（48.3 - 65.5），高风险患者为44.6%（40.2 - 48.9）（ptrend<0.0001）。两个队列的多变量分析表明，没有标准的临床风险因素可以解释或提供来自肿瘤基因表达的预后信息。该检测方法提高了I期高危肿瘤的预后准确性，超过了国家综合癌症网络标准（p<0.0001），并区分了所有疾病阶段的低风险，中等风险和高风险患者。我们的实用，定量PCR为基础的检测可靠地确定了手术切除后死亡率高的早期非鳞状NSCLC患者。加州大学旧金山分校胸部肿瘤实验室和Pinpoint基因组学。
The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.