Identification of CDKN3 and UBE2C mRNAs as Prognostic Biomarkers in Early-Stage Lung Adenocarcinoma Using Bioinformatics Strategy

Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer with very poor 5-year overall survival (OS) rate. It is histopathologically difficult to predict clinical outcome in early-stage LUAD. Identifying reliable prognostic biomarker is absolutely critical to benefit from early additional treatment for early-stage LUAD patients. The purpose of the current study was to identify critical genes as prognostic biomarkers in early-stage LUAD using gene expression profiles based on the microarray. In this bioinformatics-based cross-study, gene expression profiles from early-stage LUAD, including GSE10072 and GSE19804 genes were integrated using bioinformatics methods, including differentially expressed gene analysis (DEGA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction. Subsequently, the survival analysis of key genes was performed using The Cancer Genome Atlas (TCGA) database and was validated using online Gene Expression Profiling Interactive Analysis (GEPIA) database. A total of 89 up-regulated and 214 down-regulated genes were identified in early-stage LUAD, and the functional changes of 303 differentially expressed genes (DEGs) were mainly related to cell cycle. A PPI network was established by online STRING database with 207 nodes and 775 edges. Centrality analysis showed that CDKN3 and UBE2C genes were identified as key genes implicated in early-stage LUAD. Survival analysis revealed that low mRNA expressions of CDKN3 and UBE2C were significantly associated with longer OS of early-stage LUAD patients. This cross-study found key dysregulated genes involved in early-stage LUAD, which might provide insights into the pathogenesis of early-stage LUAD, and identified UBE2C and CDKN3 might serve as potential diagnostic and prognostic biomarkers and therapeutic targets for early-stage LUAD.