FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell Carcinoma

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.