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      Network‐based identification of key proteins and repositioning of drugs for non‐small cell lung cancer

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          Abstract

          Background

          NSCLC is a lethal cancer that is highly prevalent and accounts for 85% of cases of lung cancer. Conventional cancer treatments, such as chemotherapy and radiation, frequently exhibit limited efficacy and notable adverse reactions. Therefore, a drug repurposing method is proposed for effective NSCLC treatment.

          Aims

          This study aims to evaluate candidate drugs that are effective for NSCLC at the clinical level using a systems biology and network analysis approach.

          Methods

          Differentially expressed genes in transcriptomics data were identified using the systems biology and network analysis approaches. A network of gene co‐expression was developed with the aim of detecting two modules of gene co‐expression. Following that, the Drug–Gene Interaction Database was used to find possible drugs that target important genes within two gene co‐expression modules linked to non‐small cell lung cancer (NSCLC). The use of Cytoscape facilitated the creation of a drug–gene interaction network. Finally, gene set enrichment analysis was done to validate candidate drugs.

          Results

          Unlike previous research on repositioning drugs for NSCLC, which uses a gene co‐expression network, this project is the first to research both gene co‐expression and co‐occurrence networks. And the co‐occurrence network also accounts for differentially expressed genes in cancer cells and their adjacent normal cells. For effective management of non‐small cell lung cancer (NSCLC), drugs that show higher gene regulation and gene affinity within the drug–gene interaction network are thought to be important. According to the discourse, NSCLC genes have a lot of control over medicines like vincristine, fluorouracil, methotrexate, clotrimazole, etoposide, tamoxifen, sorafenib, doxorubicin, and pazopanib.

          Conclusion

          Hence, there is a possibility of repurposing these drugs for the treatment of non‐small‐cell lung cancer.

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          Most cited references61

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cytoscape: a software environment for integrated models of biomolecular interaction networks.

            Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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              STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

              Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
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                Author and article information

                Contributors
                omadeyemo@gmail.com
                mary.adewunmi@utas.edu.au
                Journal
                Cancer Rep (Hoboken)
                Cancer Rep (Hoboken)
                10.1002/(ISSN)2573-8348
                CNR2
                Cancer Reports
                John Wiley and Sons Inc. (Hoboken )
                2573-8348
                10 April 2024
                April 2024
                : 7
                : 4 ( doiID: 10.1002/cnr2.v7.4 )
                : e2031
                Affiliations
                [ 1 ] Department of Biochemistry Federal University of Technology Akure Nigeria
                [ 2 ] Cancer Research with AI (CaresAI) Hobart Australia
                [ 3 ] Department of Biochemistry and Nutrition Nigeria Institute of Medical Research Lagos Nigeria
                [ 4 ] College of Health and Medicine University of Tasmania Hobart Tasmania Australia
                [ 5 ] Department of Microbiology Obafemi Awolowo University Ile‐Ife Nigeria
                [ 6 ] Department of Computer Engineering, Faculty of Engineering Cairo University Cairo Egypt
                Author notes
                [*] [* ] Correspondence

                Oluwatosin Maryam Adeyemo and Mary Adewunmi, Cancer Research with AI (CaresAI), Australia.

                Email: omadeyemo@ 123456gmail.com ; mary.adewunmi@ 123456utas.edu.au

                Author information
                https://orcid.org/0000-0002-1234-5239
                https://orcid.org/0000-0003-2511-3151
                https://orcid.org/0000-0002-3727-5417
                https://orcid.org/0000-0002-7187-7112
                https://orcid.org/0000-0002-6216-9261
                https://orcid.org/0000-0002-4594-211X
                Article
                CNR22031
                10.1002/cnr2.2031
                11006715
                38600056
                8bd0b61f-a08b-48fa-9438-a6f9808e8ab5
                © 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 February 2024
                : 12 June 2023
                : 21 February 2024
                Page count
                Figures: 6, Tables: 2, Pages: 11, Words: 6100
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                April 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:10.04.2024

                drug repurposing,drug–gene interaction,network analysis,non‐small cell lung cancer (nsclc),therapeutics

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