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High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and
Ling Kui1,2,3, Min Li4, Xiaonan Yang5,6
1Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen 518067, China.
Abstract:
Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.
Insights
This study screened traditional Chinese medicines (TCM) for non-small cell lung cancer (NSCLC) treatment. Three TCMs, including *A. pierreana*, show potential as natural anticancer drugs, with identified therapeutic targets for NSCLC therapy.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer mortality worldwide.
- Conventional NSCLC treatments can have significant side effects and impact immune function.
- Traditional Chinese Medicine (TCM) combined with conventional therapies shows promise for improving NSCLC treatment efficacy.
Purpose of the Study:
- To investigate the chemical composition and antitumor mechanisms of TCM for potential NSCLC treatment.
- To identify novel natural ingredients and therapeutic targets for NSCLC using high-throughput transcriptome analysis.
Main Methods:
- Screened 78 TCMs against the NSCLC cell line (A549), generating 92 transcriptome data.
- Applied differential gene expression (DEG) and Weighted Gene Co-expression Network Analysis (WGCNA) to identify key genes and pathways.
- Utilized KEGG pathway analysis to understand the enrichment of biological pathways.
Main Results:
- *A. pierreana* treatment yielded a significant set of 6130 DEGs, with 2479 upregulated and 3651 downregulated genes.
- KEGG analysis revealed enrichment in MAPK, NF-kappa B, p53, and TGF-beta signaling pathways, with 16 significantly regulated genes.
- WGCNA identified key modules (green and darkgrey) and hub genes, and three TCMs (*B. fruticose*, *A. pierreana*, *S. scandens*) were identified as potential natural anticancer drugs.
Conclusions:
- Identified *B. fruticose*, *A. pierreana*, and *S. scandens* as promising TCMs for developing natural anticancer drugs for NSCLC.
- Determined potential therapeutic targets for NSCLC therapy through transcriptome analysis.
- This study offers novel insights into screening natural compounds for NSCLC treatment using transcriptomic data.
