Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. Methods: We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III–IV) and early (stage I–II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. Results: TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Conclusion: Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.
背景：上皮-间质转化（EMT）促进肿瘤细胞侵袭与转移。多项研究证实EMT在口腔鳞状细胞癌（OSCC）淋巴结转移中起关键作用。在EMT过程中，上皮性癌细胞丧失细胞间黏附与顶端-基底极性，获得运动性和侵袭性等间质特性。EMT的重要特征包括钙黏蛋白转换，即E-钙黏蛋白下调与N-钙黏蛋白上调。TGF-β/SMAD通路亦可诱导EMT。本研究旨在评估EMT标志物作为OSCC淋巴结转移预测因子的价值。方法：我们对TCGA数据库中159例原发性OSCC进行基因谱分析，检测EMT标志物（包括钙黏蛋白转换基因CDH1、CDH2）及TGF-β/SMAD通路基因表达。样本分为晚期（III-IV期）与早期（I-II期）两组，进行差异表达分析，并开展包含新鲜OSCC样本的独立验证研究。结果：TGF-β/SMAD通路基因（如SMAD6）在晚期肿瘤中表达上调。N-钙黏蛋白与SNAIL2在淋巴结阳性肿瘤中过表达，而角蛋白在这些组别中表达下调。结论：本研究表明EMT标志物表达与OSCC淋巴结转移相关，针对N-钙黏蛋白等调控因子开发靶向疗法可能抑制转移并改善预后。
EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma
肿瘤(癌症)患者之家