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

Oluwatosin Maryam Adeyemo; Zainab Ashimiyu-Abdusalam; Mary Adewunmi; Temitope Ayanfunke Ayano; Muhammad Sohaib; Reem Abdel-Salam

doi:10.1002/cnr2.2031

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

Cancer Rep (Hoboken). 2024 Apr;7(4):e2031. doi: 10.1002/cnr2.2031.

Authors

Oluwatosin Maryam Adeyemo^{1

2}, Zainab Ashimiyu-Abdusalam^{2

3}, Mary Adewunmi^{2

4}, Temitope Ayanfunke Ayano^{2

5}, Muhammad Sohaib², Reem Abdel-Salam^{2

6}

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.

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.

Keywords: drug repurposing; drug–gene interaction; network analysis; non‐small cell lung cancer (NSCLC); therapeutics.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / metabolism
Drug Repositioning
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism