Jing Zhao1, Chao Guo2, Zhiming Ma3, Hongsheng Liu2, Chuhu Yang4, Shanqing Li5. 1. Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China. 2. Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China. 3. Division of Research and Development, Oriomics Inc. Hangzhou, Zhejiang, 310018, China. 4. Division of Research and Development, Oriomics Inc. Hangzhou, Zhejiang, 310018, China. Electronic address: chuhu.yang@oriomics.com. 5. Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address: lidanqing@pumch.cn.
Abstract
OBJECTIVES: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Understanding the molecular mechanisms underlying tumor progression is of clinical significance. This study aimed to identify novel molecular markers associated with LUAD prognosis. MATERIALS AND METHODS: RNA sequencing data from the Cancer Genome Atlas (TCGA) database of LUAD tumors and paired normal tissues, and microarray data from the Gene Expression Omnibus (GEO) database were obtained. In the TCGA dataset, differentially expressed (DE) genes were identified by comparing gene expression between early-stage tumors and normal tissue, as well as between advanced-stage and early-stage tumors. A risk score was developed using a weighted linear combination of individual dysregulated protein-coding genes that was associated with overall survival (OS). The prognostic value of the risk score was evaluated using Kaplan-Meier and multivariate Cox analysis. The gene signature was further validated using independent datasets from GEO. RESULTS: Among the 68 identified DE genes, 19 were individually associated with OS in univariate analyses. A risk score was constructed for each patient based on the coefficients in multivariate Cox model and normalized expression levels of these 19 genes. LUAD patients with a low risk score had a significantly better survival than those with a high risk score (log-rank P < 0.0001). After adjusting for age, sex, clinical stage, smoking history, and treatments, the patients with a low risk score had a 81 % decreased risk for death, compared to those with a high risk score (hazard ratio 0.19, 95 % confidence interval 0.097-0.36). The significant association of the risk score with OS in LUAD patients was further validated in three independent GEO datasets. CONCLUSION: A novel 19-gene prognostic signature based on gene expression was identified in LUAD patients. The findings further improve the understanding of LUAD prognostication and have the potential to facilitate risk-stratified disease management.
OBJECTIVES:Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Understanding the molecular mechanisms underlying tumor progression is of clinical significance. This study aimed to identify novel molecular markers associated with LUAD prognosis. MATERIALS AND METHODS: RNA sequencing data from the Cancer Genome Atlas (TCGA) database of LUAD tumors and paired normal tissues, and microarray data from the Gene Expression Omnibus (GEO) database were obtained. In the TCGA dataset, differentially expressed (DE) genes were identified by comparing gene expression between early-stage tumors and normal tissue, as well as between advanced-stage and early-stage tumors. A risk score was developed using a weighted linear combination of individual dysregulated protein-coding genes that was associated with overall survival (OS). The prognostic value of the risk score was evaluated using Kaplan-Meier and multivariate Cox analysis. The gene signature was further validated using independent datasets from GEO. RESULTS: Among the 68 identified DE genes, 19 were individually associated with OS in univariate analyses. A risk score was constructed for each patient based on the coefficients in multivariate Cox model and normalized expression levels of these 19 genes. LUAD patients with a low risk score had a significantly better survival than those with a high risk score (log-rank P < 0.0001). After adjusting for age, sex, clinical stage, smoking history, and treatments, the patients with a low risk score had a 81 % decreased risk for death, compared to those with a high risk score (hazard ratio 0.19, 95 % confidence interval 0.097-0.36). The significant association of the risk score with OS in LUAD patients was further validated in three independent GEO datasets. CONCLUSION: A novel 19-gene prognostic signature based on gene expression was identified in LUAD patients. The findings further improve the understanding of LUAD prognostication and have the potential to facilitate risk-stratified disease management.