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FCGBP functions as a tumor suppressor gene in head and neck squamous cell carcinoma
Lijuan Zeng1,2, Jun Zeng2,3, Jianfeng He1,2
1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Medical University, 195 Dongfengxi Road, Yuexiu District, Guangzhou, China.
Purpose:
The pathogenesis of head and neck squamous cell carcinoma (HNSCC) was complex and the overall survival was not satisfying. It was urgent to uncover novel molecules that play vital role in HNSCC for disease monitoring and drug development.
Methods:
Distinguished expression of FCGBP mRNA in HNSCC was analyzed by TCGA-HNSC and three GEO datasets, the relationship between FCGBP and clinical stage and survival was analyzed by GEPIA 2, the immune infiltration pattern analysis was conducted by TIMER 2.0, pathways affected by FCGBP was conducted by GSEA and GO/KEGG. In vitro experiments (including qRT-PCR, siRNA transfection, CCK8, transwell assay and flow cytometry) were conducted to confirm bioinformatic analysis.
Results:
FCGBP was down-regulated in tumor samples compared with normal tissues at both mRNA and protein levels, and positively correlated with survival in HNSCC. Genes co-expressed with FCGBP were mainly enriched in immune-related biological processes and pathways. GSEA indicated that FCGBP was associated with activated immune reaction and inhibiting well-known pro-tumor pathways. GSE41613 validated FCGBP as an independent prognostic marker for HNSCC and FCGBP was down-regulated in HNSCC cell lines by qRT-PCR. Migration and invasion of SCC9 and CAL27 were enhanced by FCGBP-targeting siRNAs, the ratio of cytotoxic T lymphocytes were down-regulated while the ratio of myeloid-derived suppressor cells were increased by FCGBP-targeting siRNAs.
Conclusion:
FCGBP was a tumor suppressor gene and was an independent prognostic marker for better survival. The underlying mechanism may be that FCGBP inhibited tumor migration and invasion and activated immune response against tumor cells.
Insights
FCGBP acts as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC), inhibiting cancer cell migration and invasion. This gene is a promising prognostic marker for improved patient survival in HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Head and neck squamous cell carcinoma (HNSCC) presents complex pathogenesis and unsatisfactory survival rates.
- Identifying novel molecular targets is crucial for HNSCC monitoring and therapeutic development.
Purpose of the Study:
- To investigate the role of FCGBP in HNSCC pathogenesis.
- To evaluate FCGBP as a potential prognostic biomarker for HNSCC.
Main Methods:
- Bioinformatic analysis of TCGA-HNSC, GEO datasets, GEPIA 2, TIMER 2.0, GSEA, and GO/KEGG.
- In vitro validation using qRT-PCR, siRNA transfection, CCK8, transwell assays, and flow cytometry in HNSCC cell lines.
Main Results:
- FCGBP mRNA and protein were significantly down-regulated in HNSCC tissues and cell lines.
- Down-regulation of FCGBP correlated with poorer survival and was validated as an independent prognostic marker.
- FCGBP co-expression genes were enriched in immune responses; FCGBP suppressed pro-tumor pathways and inhibited cancer cell migration and invasion.
- FCGBP targeting siRNA increased myeloid-derived suppressor cells and decreased cytotoxic T lymphocytes.
Conclusions:
- FCGBP functions as a tumor suppressor gene in HNSCC.
- FCGBP is a valuable independent prognostic marker associated with better survival in HNSCC patients.
- FCGBP exerts its effects by inhibiting tumor cell migration/invasion and promoting anti-tumor immune responses.
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