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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
In silico identification of potential targets and drugs for non-small cell lung cancer
Chien-Hung Huang1, Min-You Wu1, Peter Mu-Hsin Chang2
1Department of Computer Science and Information Engineering, National Formosa University, 64, Wen-Hwa Road, Hu-wei 632, Yun-Lin, Taiwan.
Abstract:
Lung cancer is one of the leading causes of death in both the USA and Taiwan, and it is thought that the cause of cancer could be because of the gain of function of an oncoprotein or the loss of function of a tumour suppressor protein. Consequently, these proteins are potential targets for drugs. In this study, differentially expressed genes are identified, via an expression dataset generated from lung adenocarcinoma tumour and adjacent non-tumour tissues. This study has integrated many complementary resources, that is, microarray, protein-protein interaction and protein complex. After constructing the lung cancer protein-protein interaction network (PPIN), the authors performed graph theory analysis of PPIN. Highly dense modules are identified, which are potential cancer-associated protein complexes. Up- and down-regulated communities were used as queries to perform functional enrichment analysis. Enriched biological processes and pathways are determined. These sets of up- and down-regulated genes were submitted to the Connectivity Map web resource to identify potential drugs. The authors' findings suggested that eight drugs from DrugBank and three drugs from NCBI can potentially reverse certain up- and down-regulated genes' expression. In conclusion, this study provides a systematic strategy to discover potential drugs and target genes for lung cancer.
Insights
This study identifies potential lung cancer drugs by analyzing gene expression and protein interactions. It reveals eight drugs from DrugBank and three from NCBI that may reverse gene expression changes in lung adenocarcinoma.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Lung cancer is a leading cause of mortality globally.
- Cancer arises from genetic alterations affecting oncoproteins and tumor suppressor proteins.
- Identifying novel therapeutic targets and drugs is crucial for lung cancer treatment.
Purpose of the Study:
- To identify differentially expressed genes in lung adenocarcinoma.
- To construct and analyze the lung cancer protein-protein interaction network (PPIN).
- To discover potential therapeutic drugs for lung cancer.
Main Methods:
- Analysis of gene expression datasets from tumor and adjacent non-tumor tissues.
- Integration of microarray, protein-protein interaction, and protein complex data.
- Application of graph theory to PPIN analysis and functional enrichment analysis.
- Utilizing the Connectivity Map web resource for drug discovery.
Main Results:
- Identification of highly dense modules representing potential cancer-associated protein complexes.
- Determination of enriched biological processes and pathways.
- Discovery of eight drugs from DrugBank and three from NCBI with potential to reverse gene expression changes.
Conclusions:
- The study presents a systematic strategy for identifying potential drugs and target genes for lung cancer.
- Network-based analysis of gene expression and protein interactions is a viable approach for drug discovery.
- The identified drugs warrant further investigation for lung cancer therapy.
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