Analysis of genes associated with prognosis of lung adenocarcinoma based on GEO and TCGA databases

Abstract

Backgrounds: Lung adenocarcinoma (LUAD) is one of the most common malignancies, and is a serious threat to human health. The aim of the present study was to assess potential biomarkers for the prognosis of LUAD through the analysis of gene expression microarrays.

Methods: The gene expression data for GSE118370 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between normal lung and LUAD samples were screened using the R language. The DAVID database was used to analyze the functions and pathways of DEGs. The STRING database was used to the map protein-protein interaction (PPI) networks, and these were visualized with the Cytoscape software. Finally, the prognostic analysis of the hub gene in the PPI network was performed using the Kaplan-Meier tool.

Results: A total of 406 downregulated and 203 upregulated DEGs were identified. The GO analysis results revealed that downregulated DEGs were significantly enriched in angiogenesis, calcium ion binding and cell adhesion. The upregulated DEGs were significantly enriched in the extracellular matrix disassembly, collagen catabolic process, chemokine-mediated signaling pathway and endopeptidase inhibitor activity. The KEGG pathway analysis revealed that downregulated DEGs were enriched in neuroactive ligand-receptor interaction, hematopoietic cell lineage and vascular smooth muscle contraction, while upregulated DEGs were enriched in phototransduction. In addition, the top 10 hub genes and the most closely interacting modules of the top 3 proteins in the PPI network were screened. Finally, the independent prognostic value of each hub gene in LUAD patients was analyzed through the Kaplan-Meier plotter. Seven hub genes (ADCY4, S1PR1, FPR2, PPBP, NMU, PF4, and GCG) were closely correlated to overall survival time.

Conclusion: The discovery of these candidate genes and pathways reveals the etiology and molecular mechanisms of LUAD, providing ideas and guidance for the development of new therapeutic approaches to LUAD.

Figure 1

DEGs expression profile in the GEO dataset. (A) A volcano plot of 609 DEGs. Red: upregulation with |log₂fold change | > 2, P < .05; blue: downregulation with |log₂fold change | > 2, P < .05; black: unchanged genes. (B) Heatmap of the 609 DEGs with |log₂fold change | > 2, P < .05. Red: higher expression; blue: lower expression.

Figure 2

The Gene ontology and KEGG pathway analysis results for downregulated DEGs with |log₂fold change | > 2. (A) BP: biological process; (B) CC: cellular component; (C) MF: molecular function; (D) KEGG: Kyoto Encyclopedia of Genes and Genomes.

Figure 2 (Continued)

The Gene ontology and KEGG pathway analysis results for downregulated DEGs with |log₂fold change | > 2. (A) BP: biological process; (B) CC: cellular component; (C) MF: molecular function; (D) KEGG: Kyoto Encyclopedia of Genes and Genomes.

Figure 3

The Gene ontology and KEGG pathway analysis results for upregulated DEGs with |log₂fold change | > 2. (A) BP: biological process; (B) CC: cellular component; (C) MF: molecular function; (D) KEGG: Kyoto Encyclopedia of Genes and Genomes.

Figure 3 (Continued)

The Gene ontology and KEGG pathway analysis results for upregulated DEGs with |log₂fold change | > 2. (A) BP: biological process; (B) CC: cellular component; (C) MF: molecular function; (D) KEGG: Kyoto Encyclopedia of Genes and Genomes.

Figure 4

Module analysis of the PPI network. (A) module 1; (B) module 2; (C) module 3.

Figure 5

The Kaplan–Meier survival curves by mRNA expression levels of 10 hub genes of 866 LUAD patients (The log-rank P < .05 was statistically significant). (A) ADCY4; (B) S1PR1; (C) FPR2; (D) PPBP; (E) NMU; (F) PF4; (G) GCG; (H) GNGT1; (I) GPR37; (J) S1PR5.

Figure 5 (Continued)

The Kaplan–Meier survival curves by mRNA expression levels of 10 hub genes of 866 LUAD patients (The log-rank P < .05 was statistically significant). (A) ADCY4; (B) S1PR1; (C) FPR2; (D) PPBP; (E) NMU; (F) PF4; (G) GCG; (H) GNGT1; (I) GPR37; (J) S1PR5.

Figure 5 (Continued)

The Kaplan–Meier survival curves by mRNA expression levels of 10 hub genes of 866 LUAD patients (The log-rank P < .05 was statistically significant). (A) ADCY4; (B) S1PR1; (C) FPR2; (D) PPBP; (E) NMU; (F) PF4; (G) GCG; (H) GNGT1; (I) GPR37; (J) S1PR5.