GPX2 and BMP4 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...

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Main Authors: Mohammad Hossein Derakhshan Nazari, Rana Askari Dastjerdi, Parnian Ghaedi Talkhouncheh, Ahmad Bereimipour, Hamidreza Mollasalehi, Amir Ali Mahshad, Ali Razi, Mohammad Hossein Nazari, Amin Ebrahimi Sadrabadi, Sara Taleahmad
Format: Article
Language:English
Published: Royan Institute (ACECR), Tehran 2022-06-01
Series:Cell Journal
Subjects:
Online Access:https://www.celljournal.org/article_253283_d7f7e1adb03c0f7aeb1ef8aede725c30.pdf
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author Mohammad Hossein Derakhshan Nazari
Rana Askari Dastjerdi
Parnian Ghaedi Talkhouncheh
Ahmad Bereimipour
Hamidreza Mollasalehi
Amir Ali Mahshad
Ali Razi
Mohammad Hossein Nazari
Amin Ebrahimi Sadrabadi
Sara Taleahmad
author_facet Mohammad Hossein Derakhshan Nazari
Rana Askari Dastjerdi
Parnian Ghaedi Talkhouncheh
Ahmad Bereimipour
Hamidreza Mollasalehi
Amir Ali Mahshad
Ali Razi
Mohammad Hossein Nazari
Amin Ebrahimi Sadrabadi
Sara Taleahmad
author_sort Mohammad Hossein Derakhshan Nazari
collection DOAJ
description 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 NSCLCadenocarcinoma, 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 andGPX2 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.
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spelling doaj.art-fd48e4099a53415794b33db37e8fa6712022-12-22T02:05:41ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142022-06-0124630230810.22074/cellj.2022.7930253283GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics AnalysisMohammad Hossein Derakhshan Nazari0Rana Askari Dastjerdi1Parnian Ghaedi Talkhouncheh2Ahmad Bereimipour3Hamidreza Mollasalehi4Amir Ali Mahshad5Ali Razi6Mohammad Hossein Nazari7Amin Ebrahimi Sadrabadi8Sara Taleahmad9Department of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, IranDepartment of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, IranDepartment of Cell and Molecular Biology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Cell and Molecular Biology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, IranDepartment of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, IranBiophysics Department, Science Faculty, York University, Toronto, CanadaV. Zelman Institute for Medicine and Psychology, Novosibirsk State University, Novosibirsk, RussiaDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranObjective: 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 NSCLCadenocarcinoma, 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 andGPX2 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.https://www.celljournal.org/article_253283_d7f7e1adb03c0f7aeb1ef8aede725c30.pdfglutathione peroxidasein silicomicroarraynsclctgf-β signaling
spellingShingle Mohammad Hossein Derakhshan Nazari
Rana Askari Dastjerdi
Parnian Ghaedi Talkhouncheh
Ahmad Bereimipour
Hamidreza Mollasalehi
Amir Ali Mahshad
Ali Razi
Mohammad Hossein Nazari
Amin Ebrahimi Sadrabadi
Sara Taleahmad
GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
Cell Journal
glutathione peroxidase
in silico
microarray
nsclc
tgf-β signaling
title GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
title_full GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
title_fullStr GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
title_full_unstemmed GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
title_short GPX2 and BMP4 as Significant Molecular Alterations in The Lung Adenocarcinoma Progression: Integrated Bioinformatics Analysis
title_sort gpx2 and bmp4 as significant molecular alterations in the lung adenocarcinoma progression integrated bioinformatics analysis
topic glutathione peroxidase
in silico
microarray
nsclc
tgf-β signaling
url https://www.celljournal.org/article_253283_d7f7e1adb03c0f7aeb1ef8aede725c30.pdf
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