Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma.
Validation of a molecular and pathological model for five-year mortality risk in patients with early stage lung adenocarcinoma.
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DOI：
10.1097/jto.0000000000000365
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Harrison DJ
中科院分区：
文献类型：
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作者：
Bueno R;Hughes E;Wagner S;Gutin AS;Lanchbury JS;Zheng Y;Archer MA;Gustafson C;Jones JT;Rushton K;Saam J;Kim E;Barberis M;Wistuba I;Wenstrup RJ;Wallace WA;Hartman AR;Harrison DJ
本研究的目的是验证一种分子表达特征[细胞周期进展（CCP）评分]，该评分在一个大型患者队列中识别早期（I-II）肺腺癌手术切除后癌症相关死亡风险较高的患者，并评估CCP评分和病理分期相结合预测肺癌死亡率的有效性。采用实时荧光定量聚合酶链反应对650例ⅰ、ⅱ期腺癌患者进行福尔马林固定石蜡包埋手术肿瘤标本进行31个增殖基因的分析。以5年肺癌特异性死亡为主要结局，通过Cox比例风险分析评估表达评分的预后区别。CCP评分是肺癌特异性死亡率高于临床协变量的显著预测因子[每四分位数范围的风险比(HR) = 1.46(95%可信区间= 1.12-1.90;p = 0.0050)]。在全队列中（HR = 2.01, p = 2.8 × 10−11）和I期患者（HR = 1.67, p = 0.00027）， CCP评分与病理分期相结合的预后评分是肺癌死亡风险的更重要指标。以预后评分的第85百分位为阈值，低危患者组和高危患者组的肺癌生存率存在显著差异（p = 3.8 × 10−7）。本研究验证了CCP评分和预后评分作为单纯手术治疗的早期肺腺癌患者肺癌死亡的独立预测因子。切除的I期肺腺癌患者和预后评分高的患者可能是辅助治疗的候选人，以降低癌症相关的死亡率。
The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality.