A Robust 8-Gene Prognostic Signature for Early-Stage Non-small Cell Lung Cancer
A Robust 8-Gene Prognostic Signature for Early-Stage Non-small Cell Lung Cancer
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DOI：
10.3389/fonc.2019.00693
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发表时间：
2019-07-31
影响因子：
4.7
通讯作者：
Zuo, Shuguang
中科院分区：
文献类型：
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作者：
He, Ru;Zuo, Shuguang
背景：目前的分期系统对早期非小细胞肺癌（NSCLC）的预后预测不准确。本研究旨在为早期NSCLC开发一个稳健的预后特征，从而对预后不良的高风险患者进行分类，并做出具体的治疗决策。方法：在本研究中，使用来自基因表达综合数据集（GEO）的早期NSCLC患者数据的回顾性汇总进行了全面的全基因组分析，包括GSE 31210，GSE 37745，和GSE 50081和癌症基因组图谱（TCGA）。实施考克斯比例风险模型以确定每个数据集中基因表达水平与总体患者存活率之间的关联。所有数据集中的共同基因被选为候选预后基因。使用四个独立的数据集和整个队列开发并验证了风险评分模型。采用Kaplan-Meier对数秩检验评估生存差异。每个数据集的单变量考克斯比例风险回归分析显示，GSE 31210中总共2280个基因、GSE 37745中762个基因、GSE 50081中871个基因和TCGA中666个基因被鉴定为候选保护基因，而GSE 31210中总共2131个基因，GSE 37745中的913、GSE 50081中的1107和TCGA中的997被确定为候选风险基因。与总生存期相关的共有基因有8个，其中mRNA 7个，lncRNA 1个。通过逐步多变量考克斯分析，建立了早期NSCLC的8个基因预后标记（CDCP 1、HMMR、TPX 2、CIRBP、HLF、KBTBD 7、SEC 24 B-AS 1和SH 2B 1）。高风险组患者的总生存期短于低风险组。多因素回归和分层分析表明，8基因标签的预后能力与其他临床因素无关。此外，8-基因签名在GSE 31210、GSE 37745、GSE 50081和TCGA中分别实现0.726、0.701、0.725和0.650的AUC值。此外，相结合的8-基因签名和阶段导致一个更好的患者分类的生存预测和治疗decision.Conclusion：这项研究开发了一个强大的基因签名具有很大的价值，在早期NSCLC的预后预测，这可能有助于患者分类和个性化的治疗决策。
Background: The current staging system is imprecise for prognostic prediction of early-stage non-small cell lung cancer (NSCLC). This study aimed to develop a robust prognostic signature for early-stage NSCLC, allowing classification of patients with a high risk of poor outcome and specific treatment decision.Method: In the present study, a comprehensive genome-wide profiling analysis was conducted using a retrospective pool of early-stage NSCLC patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE31210, GSE37745, and GSE50081 and The Cancer Genome Atlas (TCGA). Cox proportional hazards models were implemented to determine the association between gene expression levels and overall patient survival in each dataset. The common genes among all datasets were selected as candidate prognostic genes. A risk scoremodel was developed and validated using four independent datasets and the entire cohort. The Kaplan-Meier with log-rank test was used to assess survival difference.Results: A univariate Cox proportional hazards regression analysis for each dataset showed that a total of 2280 genes in GSE31210, 762 genes in GSE37745, 871 genes in GSE50081, and 666 genes in TCGA were identified as candidate protective genes, while overall 2131 genes in GSE31210, 913 in GSE37745, 1107 in GSE50081, and 997 in TCGA were identified as candidate risky genes. There were 8 common genes associated with overall survival, including 7mRNA and 1 lncRNA. By using the Step-wisemultivariate Cox analysis, an 8-gene prognostic signature (CDCP1, HMMR, TPX2, CIRBP, HLF, KBTBD7, SEC24B-AS1, and SH2B1) for early-stage NSCLC was developed. Patients in the high-risk group had shorter overall survival than those in the low-risk group. Multivariate regression and stratified analysis suggested that the prognostic power of the 8-gene signature was independent of other clinical factors. Furthermore, the 8-gene signature achieved AUC values of 0.726, 0.701, 0.725 and 0.650 in GSE31210, GSE37745, GSE50081 and TCGA, respectively. Moreover, the combination of the 8-gene signature and the stage resulted to a better patient classification for survival prediction and treatment decision.Conclusion: This study developed a robust gene signature with great value for prognostic prediction in early-stage NSCLC, which may contribute to patient classification and personalized treatment decisions.