entification of Key Biomarkers and CandidateMolecules in Lung Cancer via Bioinformatics Analysis

Background: lung cancer is a major cause of cancer deathsworldwide. Although deaths from lung cancer have declineddramatically during recent years, it is still the second mostcommonly diagnosed cancer and is responsible for most cancer deaths in both sexes. In the present study, hub genes were identifiedand molecular mechanisms were revealed in lung cancer.Materials and Methods: Gene expression profiles were analyzedusing GSE۱۹۸۰۴ from the GEO datasets. GEO۲R toolwas used for Gene Expression Analysis and obtaining the DifferentiallyExpressed Genes (DEGs). Adj. p-value < ۰.۰۱ andlog۲FC (fold change) >۱ were considered as the cut-off criteria.DAVID database was used toreveal enrichment analysis onthe DEGs. The gene pathways with overlapping functions wereidentified in the KEGG database. The protein-protein interactionnetwork graph (PPI) was obtained using the STRING databaseto analyze the interactions between DEGs.Results: ۱۲۰ DEGs were identified; KEGG and DAVID databasesshowed that SPP۱ gene (encoding secreted phosphoprotein۱) was identified as a upregulated gene in lung cancer.Secreted phosphoprotein ۱ is an extracellular matrix (ECM)protein, which interacts with a number of adhesion receptorbinding motifs including a C-terminal CD۴۴v۶ domain andthrombin-cleaved N-terminal integrin domains. Therefore,SPP۱ gene is involved in cell adhesion and other similar signalingpathways and promotes tumor progression and metastasis.Hsa-miR-۲۵-۵p could also exert a suppressive effect on theSPP۱ gene’s activity by acting as a gene expression regulator.Conclusion: SPP۱ gene, can participate in extracellular matrix(ECM)-receptor interactions and the focal adhesion responsepathway to regulate tumor metastasis and invasion. Specificinteractions between cells and the ECM are mediated by transmembranemolecules, mainly integrins and perhaps also proteoglycans,CD۳۶, or other cell-surface-associated components.These interactions lead to a direct or indirect control of cellularactivities such as adhesion, migration, differentiation, proliferation,and apoptosis. The SPP۱ silencing strategy could bea potential approach to improve the prognosis of lung cancerpatients.