Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung
Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lung
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DOI：
10.1158/1078-0432.ccr-08-0576
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发表时间：
2008-08-01
影响因子：
11.5
通讯作者：
Rosell, Rafael
中科院分区：
文献类型：
--
作者：
Skrzypski, Marcin;Jassem, Ewa;Rosell, Rafael
目的：辅助治疗可提高早期肺鳞状细胞癌（SCC）的生存率;然而，绝对获益不大，主要限于II-IIIA期。目前的分期方法是不精确的预后指标，但高风险的患者可以通过基因表达谱和考虑辅助therapy.Experimental Design：29个基因的表达进行了评估，从66例SCC患者接受手术切除的冷冻原发性肿瘤标本中获得的逆转录酶定量PCR。使用中位数作为截止值对表达值进行二分。我们使用的风险评分，以开发一个基因表达模型的预测survival.Results：在训练队列中的基因表达的单变量分析确定了10个基因具有显着的预后价值：CSF 1，EGFR，CA IX，PH 4，KIAA 0974，ANLN，VEGFC，NTRK 1，FN 1，和INR 1。在多变量考克斯模型中，CSF 1（风险比，3.5; P = 0.005）、EGFR（风险比，2.7; P = 0.02）、CA IX（风险比，0.2; P < 0.0001）和肿瘤大小>4 cm（风险比，2.7; P = 0.02）是生存的重要标志物。基于三个基因（CSF 1，EGFR和CA IX）表达的风险评分的高预后价值在一个独立的实验室中的26例患者的单独队列中得到了积极验证（P = 0.05）。结论：三个基因签名与早期SCC的预后密切相关。阳性独立验证表明其适用于选择可能受益于辅助治疗的死亡风险增加的SCC患者。
Purpose: Adjuvant treatment may improve survival in early-stage squamous cell carcinoma (SCC) of the lung; however, the absolute gain is modest and mainly limited to stage II-IIIA. Current staging methods are imprecise indications of prognosis, but high-risk patients can be identified by gene expression profiling and considered for adjuvant therapy.Experimental Design:The expression of 29 genes was assessed by reverse transcriptase quantitative PCR in frozen primary tumor specimens obtained from 66 SCC patients who had undergone surgical resection. Expression values were dichotomized using the median as a cutoff value. We used a risk score to develop a gene expression model for the prediction of survival.Results: The univariate analysis of gene expression in the training cohort identified 10 genes with significant prognostic value: CSF1, EGFR, CA IX, PH4, KIAA 0974, ANLN, VEGFC, NTRK1, FN1, and INR1. In the multivariate Cox model, CSF1 (hazard ratio, 3.5; P = 0.005), EGFR (hazard ratio, 2.7; P = 0.02), CA IX (hazard ratio, 0.2; P < 0.0001), and tumor size >4 cm (hazard ratio, 2.7; P = 0.02) emerged as significant markers for survival. The high prognostic value of a risk score based on the expression of the three genes (CSF1, EGFR, and CA IX) was positively validated in a separate cohort of 26 patients in an independent laboratory (P = 0.05).Conclusions: The three-gene signature is strongly associated with prognosis in early-stage SCC. Positive independent validation suggests its suitability for selecting SCC patients with an increased risk of death who might benefit from adjuvant treatment.