Network-based Identification of Key Proteins and Repositioning of Drugs
for Non-Small Cell Lung Cancer
Abstract
NSCLC is a highly prevalent cancer 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. This study aims to evaluate candidate drugs
that are effective for NSCLC at the clinical level using systems biology
and network analysis approach. Differentially expressed genes of
transcriptomics data were identified using the systems biology and
network analysis approach. A network of gene co-expression was developed
with the aim of detecting two modules of gene co-expression.
Subsequently, the Drug-Gene interaction database was employed to
pinpoint potential pharmaceutical agents that target crucial genes
within two gene co-expression modules associated with non-small cell
lung cancer (NSCLC). The construction of a drug-gene interaction network
was facilitated with the utilisation of Cytoscape. Finally, the gene set
enrichment analysis was done to validate candidate drugs. 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. Drugs exhibiting elevated gene regulation
and gene affinity within the drug-gene interaction network are deemed
noteworthy for the efficacious management of non-small cell lung cancer
(NSCLC). According to this discourse, NSCLC genes exert a high degree of
regulation over medications such as vincristine, fluorouracil,
methotrexate, clotrimazole, etoposide, tamoxifen, sorafenib,
doxorubicin, and pazopanib. Hence, there is a possibility of repurposing
these drugs for the treatment of non-small cell lung cancer. Key words:
Non-small cell lung cancer (NSCLC), drug repurposing, network analysis,
drug-gene interaction, therapeutics