Abstract
Background: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. To date, the prognosis of patients with LUAD remains dismal. Methods: Three datasets were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained. FunRich was used to perform pathway enrichment analysis. Protein–protein interaction (PPI) networks were established and hub genes were obtained by Cytoscape software. GEPIA was utilized to conduct correlation and survival analysis. Upstream miRNAs of DEGs were predicted via miRNet database, and methylation status of promoters of DEGs was determined through UALCAN database. Results: A total of 375 DEGs, including 105 and 270 up-regulated and down-regulated genes in LUAD, were commonly appeared in three datasets. These DEGs were significantly enriched in mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT). About 8 up-regulated and 5 down-regulated DEGs were commonly appeared in EMT/MET-related gene set and the top 50 hub gene set. Among the 13 genes, increased expression of KRT8 and KRT19 indicated unfavorable prognosis whereas high expression of DCN and CXCL12 suggested favorable prognosis in LUAD. Correlation analysis showed that KRT8 (DCN) expression was linked to KRT19 (CXCL12) expression. Further analysis displayed that KRT8 and KRT19 could jointly forecast poor prognosis in LUAD. About 42 and 2 potential miRNAs were predicted to target KRT8 and KRT19, respectively. Moreover, methylation level analysis demonstrated that KRT8 and KRT19 were significantly hypomethylated in LUAD compared with normal controls. Conclusions: All these findings suggest that KRT8 and KRT19 are hypomethylated and overexpressed in LUAD and associated with unfavorable prognosis.
Highlights
Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer
The dataset GSE7670 based on the platform of GPL96 (Affymetrix Human Genome U133A Array) containing 27 LUAD samples and 27 normal samples, the dataset GSE10072 based on the platform of GPL96 (Affymetrix Human Genome U133A Array) containing 58 LUAD samples and 49 normal samples, the dataset GSE32863 based on the platform of GPL6884 (Illumina HumanWG-6 v3.0 expression beadchip) containing 58 LUAD tissues and 58 matched adjacent normal lung tissues, were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database
GEO2R analysis for GSE7670 found out 2048 Differentially expressed genes (DEGs), in which 913 genes were up-regulated and 1135 genes were down-regulated (Figure 1B); GEO2R analysis for GSE10072 found out 855 DEGs, in which 296 genes were up-regulated and 559 genes were down-regulated (Figure 1C); GEO2R analysis for GSE32863 found out 1428 DEGs, in which 550 genes were up-regulated and 878 genes were down-regulated (Figure 1D)
Summary
Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. To date, the prognosis of patients with LUAD remains dismal. Results: A total of 375 DEGs, including 105 and 270 up-regulated and down-regulated genes in LUAD, were commonly appeared in three datasets. These DEGs were significantly enriched in mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT). Among the 13 genes, increased expression of KRT8 and KRT19 indicated unfavorable prognosis whereas high expression of DCN and CXCL12 suggested favorable prognosis in LUAD. Correlation analysis showed that KRT8 (DCN) expression was linked to KRT19 (CXCL12) expression. Methylation level analysis demonstrated that KRT8 and KRT19 were significantly hypomethylated in LUAD compared with normal controls. Lung adenocarcinoma (LUAD), the most common histological type of lung cancer, has been a serious human health problem.
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