A Unique Gene Signature Predicting Recurrence Free Survival in Stage IA Lung Adenocarcinoma.

Autor:	Carr SR; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Wang H; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Hudlikar R; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Lu X; State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China., Zhang MR; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Hoang CD; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Yan F; State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China., Schrump DS; Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	The Journal of thoracic and cardiovascular surgery [J Thorac Cardiovasc Surg] 2023 Apr; Vol. 165 (4), pp. 1554-1564. Date of Electronic Publication: 2022 Sep 24.
DOI:	10.1016/j.jtcvs.2022.09.028
Abstrakt:	Objective: 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. Methods: 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. Results: 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). Conclusions: 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. Competing Interests: All authors have no conflicts of interest to report.
Databáze:	MEDLINE
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