医学
腺癌
比例危险模型
危险系数
基因签名
肿瘤科
生存分析
单变量
内科学
阶段(地层学)
置信区间
基因
癌症
基因表达
多元统计
生物
统计
遗传学
古生物学
数学
作者
Shamus R. Carr,Haitao Wang,Rasika R. Hudlikar,Xin Lu,Mary R. Zhang,Chuong D. Hoang,Fangrong Yan,David S. Schrump
标识
DOI:10.1016/j.jtcvs.2022.09.028
摘要
Resected stage IA lung adenocarcinoma (LUAD) has a reported 5-year recurrence free survival (RFS) of 63-81%. A unique gene signature stratifying patients with early stage LUAD as high or low-risk of recurrence would be valuable.GEO datasets combining European and North American LUAD patients (n=684) were filtered for stage IA (n=105) to develop a robust signature for recurrence (RFSscore). Univariate Cox proportional hazard regression model was used to assess associations of gene expression with RFS and OS. Leveraging a bootstrap approach of these identified upregulated genes allowed construction of a model which was evaluated by Area Under the Received Operating Characteristics. The optimal signature has RFSscore calculated via a linear combination of expression of selected genes weighted by the corresponding Cox regression derived coefficients. Log-rank analysis calculated RFS and OS. Results were validated using the LUAD TCGA transcriptomic NGS based dataset.Rigorous bioinformatic analysis identified a signature of 4 genes: KNSTRN, PAFAH1B3, MIF, CHEK1. Kaplan-Meier analysis of stage IA LUAD with this signature resulted in 5-year RFS for low-risk of 90% compared to 53% for high-risk (HR 6.55, 95%CI 2.65-16.18, p-value <0.001), confirming the robustness of the gene signature with its clinical significance. Validation of the signature using TCGA dataset resulted in an AUC of 0.797 and 5-year RFS for low and high-risk stage IA patients being 91% and 67%, respectively (HR 3.44, 95%CI 1.16-10.23, p-value=0.044).This 4 gene signature stratifies European and North American patients with pathologically confirmed stage IA LUAD into low and high-risk groups for OS and more importantly RFS.
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