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Updated: Aug 4, 2025

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Identification of hub genes and pathways in lung metastatic colorectal cancer
Wei Dai1, Caiyao Guo2, Yu Wang2
1School of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Background:
Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis.
Methods:
The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein-protein interaction (PPI) network among DEGs.
Results:
The DEGs were enriched in surfactant metabolism, cell-cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC.
Conclusion:
This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.
Insights
This study identifies key genes like CLU, SFTPD, and CCL18 involved in colorectal cancer (CRC) lung metastasis. Understanding these molecular mechanisms may lead to new therapeutic targets for metastatic CRC.
Area of Science:
- Oncology
- Bioinformatics
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a prevalent malignancy.
- Lung metastasis is a major cause of CRC mortality, poorly understood.
- Limited therapeutic targets exist for metastatic CRC.
Purpose of the Study:
- Identify key genes and molecular processes in CRC lung metastasis.
- Elucidate mechanisms driving lung tropism in CRC.
- Discover potential therapeutic targets for metastatic CRC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) database and GEO2R for differentially expressed genes (DEGs).
- Performed Gene Ontology (GO), KEGG, and Reactome analyses for pathway enrichment.
- Constructed protein-protein interaction (PPI) network using STRING and Cytoscape.
Main Results:
- DEGs enriched in surfactant metabolism, cell-cell communication, and chemokine signaling pathways.
- Identified hub genes: CLU, SFTPD, CCL18, SPP1, APOE, BGN, MMP3.
- CLU, SFTPD, and CCL18 implicated in CRC lung tropism; SFTPD promotes proliferation and metastasis.
Conclusions:
- Bioinformatics approach provides insights into CRC lung metastasis mechanisms.
- Identified candidate therapeutic targets for managing CRC lung metastasis.
- Findings may advance understanding and treatment of metastatic colorectal cancer.
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