and as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis.

Objective: Non-small cell lung adenocarcinoma (NSCLC) is the most common type of lung cancer, which is considered as the most lethal and prevalent cancer worldwide. Recently, molecular changes have been implicated to play a significant role in the cancer progression. Despite of numerous studies, the molecular mechanism of NSCLC pathogenesis in each sub-stage remains unclear. Studying these molecular alterations gives us a chance to design successful therapeutic plans which is aimed in this research.

Materials And Methods: In this bioinformatics study, we compared the expression profile of 7 minor stages of NSCLC adenocarcinoma, including GSE41271, GSE42127, and GSE75037, to clarify the relation of molecular alterations and tumorigenesis. At first, 99 common differentially expressed genes (DEG) were obtained. Then, functional enrichment analysis and protein-protein interaction (PPI) network construction were performed to uncover the association of significant cellular and molecular changes. Finally, gene expression profile interactive analysis (GEPIA) was employed to validate the results by RNA-seq expression data.

Results: Primary analysis showed that was downregulated through the tumor progression to the stage IB and was upregulated in the course of final tumor development to the stage IV and distant metastasis. Functional enrichment analysis indicated that in the TGF-β signaling pathway and in the glutathione metabolism pathway may be the key genes for NSCLC adenocarcinoma progression. GEPIA analysis revealed a correlation between downregulation and upregulation and lung adenocarcinoma (LUAD) progression and lower survival chances in LUAD patients which confirm microarray data.

Conclusion: Taken together, we suggested as an oncogene by inhibiting apoptosis, promoting EMT and increasing glucose uptake in the final stages and BMP4 as a tumor suppressor via inducing apoptosis and arresting cell cycle in the early stages through lung adenocarcinoma (ADC) development to make them candidate genes to further cancer therapy investigations.