Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma.
Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma.
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DOI：
10.18632/oncotarget.9129
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发表时间：
2016-06-07
期刊：
影响因子：
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通讯作者：
Adusumilli PS
中科院分区：
文献类型：
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作者：
Eguchi T;Kadota K;Chaft J;Evans B;Kidd J;Tan KS;Dycoco J;Kolquist K;Davis T;Hamilton SA;Yager K;Jones JT;Travis WD;Jones DR;Hartman AR;Adusumilli PS
我们研究的目的是(a)验证分子表达特征（细胞周期进展[CCP]评分和分子预后评分[mPS； CCP和病理分期{IA或IB}的结合]），以确定I期肺腺癌（ADC）患者在治疗意图手术切除后癌症特异性死亡风险较高，(b)确定mPS是否对I期肺ADC组织学亚型的预后进行分层。采用定量RT-PCR对1200例经福尔马林固定、石蜡包埋的I期肺ADC肿瘤样本进行31个增殖基因的分析。以5年肺癌特异性死亡率为主要终点，采用Cox比例风险回归评估CCP评分和mPS的预后区别。在多变量分析中，CCP评分是5年肺癌特异性死亡率的预后指标（HR=1.6 /四分位数范围；95% CI, 1.14-2.24； P=0.006）。在包括mPS而不是CCP的多变量模型中，mPS是5年肺癌特异性死亡率的重要预后指标（HR=1.77; 95% CI, 1.18-2.66； P=0.006）。5年肺癌特异性生存率在低风险和高风险mPS组之间存在差异（96% vs 81%； P<0.001）。在腺泡和乳头状亚型的中度肺ADC患者中，与低mPS相比，高mPS与更差的5年肺癌特异性生存率相关（P分别<0.001和0.015）。本研究验证了CCP评分和mPS作为肺癌特异性死亡率的独立预后指标，并为仅接受手术治疗的I期肺ADC患者提供了独立于已知高危特征的定量风险评估。
The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome. In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P=0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival (P<0.001 and 0.015, respectively), compared with low mPS. This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.