Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi 563000, China.
Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi 563006, China.
Comb Chem High Throughput Screen. 2023;26(3):539-558. doi: 10.2174/1386207325666220509191153.
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.
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.
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.
The FAM3 family may be applied as a biomarker and potential therapeutic target for HNSCC.
尽管头颈部鳞状细胞癌（HNSCC）是一种常见的恶性肿瘤，但发生和发展的分子生物学特征仍知之甚少。家族与序列相似（FAM）蛋白家族包括四个家族成员，即 FAM3A、FAM3B、FAM3C 和 FAM3D。特别是 FAM3C 先前被报道与多种人类恶性肿瘤密切相关。
通过联合使用癌症基因组图谱（TCGA）、基因表达谱交互分析（GEPIA）、肿瘤免疫估计资源（TIMER）和 MethSurv 数据库，结合基因本体论（GO）和京都基因与基因组百科全书（KEGG）生物信息学工具，探究 FAM3 家族在 HNSCC 中可能的生物学功能和关键调控途径。
高表达 FAM3A 可增加 HNSCC 线粒体生物合成和能量代谢，抑制 HNSCC 肿瘤微环境中免疫细胞浸润，并与不良预后相关。相反，FAM3B 在 HNSCC 中的低表达与 HNSCC 患者的预后较差相关。这很可能是因为 FAM3B 可以通过增加免疫细胞浸润、抑制上皮-间充质转化（EMT）和细胞色素 P450 途径来抑制 HNSCC 的发展。FAM3C 在口腔鳞状细胞癌（OSCC）中过表达，并与增加 OSCC 细胞干性、免疫逃避和 EMT 相关。在本研究中，FAM3C 通过抑制肿瘤免疫细胞浸润与 HNSCC 患者的不良预后相关。FAM3C 的表达与上皮和间充质标志物如 E-钙粘蛋白、N-钙粘蛋白、波形蛋白和 ZO-1 的表达呈正相关，这可能促进 HNSCC 中部分 EMT 状态，并大大增加其恶性程度。FAM3D 是 HNSCC 上皮表型的维持因子，可抑制 EMT 进展，促进肿瘤免疫细胞浸润，抑制 HNSCC 进展。此外，FAM3 基因家族的甲基化水平与 HNSCC 的总生存率相关。
FAM3 家族可作为 HNSCC 的生物标志物和潜在治疗靶点。
