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Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung
Song Xu1,2, Renwang Liu1,2, Yurong Da3
1Department of Lung Cancer Surgery, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Background:
This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment.
Methods:
Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug-pathway network for LUAD was constructed, and molecular docking was carried out.
Results:
After the integration of 57 LUAD-related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD-related oncogenic pathways were involved in the LUAD drug-pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly.
Conclusion:
Our study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG-028671, may have potential roles for LUAD treatment but require further experimental verification.
Insights
Researchers identified key signaling pathways, including the p53 pathway, for lung adenocarcinoma (LUAD) treatment. Several compounds show potential for targeting LUAD, with CHEK1 identified as a significant hub gene for further investigation.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Lung adenocarcinoma (LUAD) is a major cause of cancer mortality.
- Identifying novel therapeutic targets and agents for LUAD is crucial.
- Understanding tumor-related signaling pathways is key to developing effective treatments.
Purpose of the Study:
- To compare LUAD-related signaling pathways with known compounds.
- To identify potential therapeutic agents for lung adenocarcinoma.
- To elucidate the role of specific pathways and genes in LUAD progression.
Main Methods:
- Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using TCGA and GTEx data.
- Comparison with known compounds via the Connectivity Mapping dataset.
- Data mining for clinical significance of hub genes and construction of a drug-pathway network.
Main Results:
- Five overlapping pathways were identified, with the p53 signaling pathway being most significant.
- CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 were identified as hub genes within the p53 pathway.
- A network of 88 molecules targeting LUAD pathways was constructed; daunorubicin, mycophenolic acid, and pyrvinium show potential for targeting CHEK1.
Conclusions:
- The p53 signaling pathway is a critical target for LUAD treatment.
- Specific compounds like ciclopirox and AG-028671 warrant further investigation for LUAD therapy.
- This study provides a foundation for developing targeted therapies for lung adenocarcinoma.
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