TY - JOUR

T1 - GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis

AU - Nazari, Mohammad Hossein Derakhshan

AU - Dastjerdi, Rana Askari

AU - Talkhouncheh, Parnian Ghaedi

AU - Bereimipour, Ahmad

AU - Mollasalehi, Hamidreza

AU - Mahshad, Amir Ali

AU - Razi, Ali

AU - Nazari, Mohammad Hossein

AU - Sadrabadi, Amin Ebrahimi

AU - Taleahmad, Sara

N1 - Publisher Copyright: © 2022 Royan Institute (ACECR). All rights reserved.

PY - 2022/6

Y1 - 2022/6

N2 - 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 BMP4 was downregulated through the tumor progression to the stage IB and GPX2 was upregulated in the course of final tumor development to the stage IV and distant metastasis. Functional enrichment analysis indicated that BMP4 in the TGF-β signaling pathway and GPX2 in the glutathione metabolism pathway may be the key genes for NSCLC adenocarcinoma progression. GEPIA analysis revealed a correlation between BMP4 downregulation and GPX2 upregulation and lung adenocarcinoma (LUAD) progression and lower survival chances in LUAD patients which confirm microarray data. Conclusion: Taken together, we suggested GPX2 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.

AB - 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 BMP4 was downregulated through the tumor progression to the stage IB and GPX2 was upregulated in the course of final tumor development to the stage IV and distant metastasis. Functional enrichment analysis indicated that BMP4 in the TGF-β signaling pathway and GPX2 in the glutathione metabolism pathway may be the key genes for NSCLC adenocarcinoma progression. GEPIA analysis revealed a correlation between BMP4 downregulation and GPX2 upregulation and lung adenocarcinoma (LUAD) progression and lower survival chances in LUAD patients which confirm microarray data. Conclusion: Taken together, we suggested GPX2 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.

KW - Glutathione Peroxidase

KW - In Silico

KW - Microarray

KW - NSCLC

KW - TGF-β Signaling

UR - http://www.scopus.com/inward/record.url?scp=85136194876&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/ab0e4f53-36e2-3ef2-96b8-3c4e43290eda/

U2 - 10.22074/cellj.2022.7930

DO - 10.22074/cellj.2022.7930

M3 - Article

C2 - 35892234

AN - SCOPUS:85136194876

VL - 24

SP - 302

EP - 308

JO - Cell Journal

JF - Cell Journal

SN - 2228-5806

IS - 6

ER -