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Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer
Published on: February 9, 2024
FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell Carcinoma
Chengcheng Liao1,2, Qian Wang2,3, Jiaxing An4
1Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi 563000, China.
Background:
Although head and neck squamous cell carcinoma (HNSCC) is a common malignancy, the molecular biology landscape underlying its occurrence and development remains poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been previously reported to be closely associated with various human malignancies.
Methods:
Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible biological function and key pathways regulated by the FAM3 family in HNSCC were probed.
Results:
High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration, inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway. FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell infiltration. FAM3C expression was also positively correlated with the expression of epithelial and mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the FAM3 gene family were correlated with the overall survival rate of HNSCC.
Conclusion:
The FAM3 family may be applied as a biomarker and potential therapeutic target for HNSCC.
Insights
The FAM3 gene family plays a crucial role in head and neck squamous cell carcinoma (HNSCC) development. Differential expression of FAM3A, FAM3B, FAM3C, and FAM3D impacts tumor progression, immune infiltration, and patient prognosis, suggesting potential as biomarkers and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a common cancer with poorly understood molecular drivers.
- The family with sequence similarity (FAM) 3 protein family (FAM3A-D) is implicated in various human malignancies.
- FAM3C has known associations with several types of cancer.
Purpose of the Study:
- To investigate the role and potential of the FAM3 family in HNSCC.
- To explore the molecular functions and key pathways regulated by FAM3 proteins in HNSCC.
- To assess the prognostic significance of FAM3 family members in HNSCC.
Main Methods:
- Utilized The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, and MethSurv databases.
- Employed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for bioinformatics analysis.
- Correlated FAM3 gene family expression and methylation with HNSCC patient data and clinical outcomes.
Main Results:
- FAM3A overexpression correlated with increased HNSCC energy metabolism, reduced immune infiltration, and poor prognosis.
- Lower FAM3B expression was linked to poorer HNSCC prognosis, potentially via increased immune infiltration and inhibition of epithelial-mesenchymal transition (EMT).
- FAM3C overexpression was associated with HNSCC stemness, immune escape, EMT, and poor prognosis, while FAM3D inhibited EMT and promoted immune infiltration.
Conclusions:
- The FAM3 gene family exhibits diverse roles in HNSCC progression and immune modulation.
- FAM3 family members' expression levels and methylation status correlate with patient survival.
- The FAM3 family represents a promising avenue for HNSCC biomarker development and targeted therapy.
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