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Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis

Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrate...

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Autores principales: Mosharaf, Md. Parvez, Reza, Md. Selim, Gov, Esra, Mahumud, Rashidul Alam, Mollah, Md. Nurul Haque
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143695/
https://www.ncbi.nlm.nih.gov/pubmed/35632527
http://dx.doi.org/10.3390/vaccines10050771
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author Mosharaf, Md. Parvez
Reza, Md. Selim
Gov, Esra
Mahumud, Rashidul Alam
Mollah, Md. Nurul Haque
author_facet Mosharaf, Md. Parvez
Reza, Md. Selim
Gov, Esra
Mahumud, Rashidul Alam
Mollah, Md. Nurul Haque
author_sort Mosharaf, Md. Parvez
collection PubMed
description Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (CDK1, EGFR, FYN, UBC, MYC, CCNB1, FOS, RHOB, CDC6, CDC20, and CHEK1) as the hub-DEGs (potential key genes) by the protein–protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (FOXC1, GATA2, YY1, and NFIC) and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatment.
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spelling pubmed-91436952022-05-29 Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis Mosharaf, Md. Parvez Reza, Md. Selim Gov, Esra Mahumud, Rashidul Alam Mollah, Md. Nurul Haque Vaccines (Basel) Article Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (CDK1, EGFR, FYN, UBC, MYC, CCNB1, FOS, RHOB, CDC6, CDC20, and CHEK1) as the hub-DEGs (potential key genes) by the protein–protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (FOXC1, GATA2, YY1, and NFIC) and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatment. MDPI 2022-05-12 /pmc/articles/PMC9143695/ /pubmed/35632527 http://dx.doi.org/10.3390/vaccines10050771 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mosharaf, Md. Parvez
Reza, Md. Selim
Gov, Esra
Mahumud, Rashidul Alam
Mollah, Md. Nurul Haque
Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title_full Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title_fullStr Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title_full_unstemmed Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title_short Disclosing Potential Key Genes, Therapeutic Targets and Agents for Non-Small Cell Lung Cancer: Evidence from Integrative Bioinformatics Analysis
title_sort disclosing potential key genes, therapeutic targets and agents for non-small cell lung cancer: evidence from integrative bioinformatics analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143695/
https://www.ncbi.nlm.nih.gov/pubmed/35632527
http://dx.doi.org/10.3390/vaccines10050771
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