Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations, including changes attributable to the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin, and vimentin, with a focus on their roles in the invasive metastatic progression of OSCC and their potential utility in predicting prognosis. Methods: We conducted an immunohistochemical analysis to assess the protein expression profiles of Cx43, EMMPRIN, E-cadherin, and vimentin using tissue samples obtained from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROIs), including adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). The primary clinical endpoints were disease-free survival (DFS) and overall survival (OS). Results: Substantial changes in the expression profiles of the different marker proteins were observed among the different ROIs, with allp-values < 0.05, signifying statistical significance. Multivariable Cox regression analysis results showed a significant effect of increased EMMPRIN expression toward the IF on DFS (p= 0.019) and OS (p= 0.023). Furthermore, the combined predictive analysis showed a significant predictive value of the marker system for DFS (p= 0.0017) and OS (p= 0.00044). Conclusions: The combined marker system exhibited a significant ability to predict patient prognosis. An increase in EMMPRIN expression toward the IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.
背景：转移性口腔鳞状细胞癌（OSCC）与患者不良预后相关。转移是一个复杂的过程，涉及多种蛋白质、肿瘤细胞改变（包括上皮-间质转化（EMT）过程引起的变化）以及与肿瘤微环境（TME）的相互作用。本研究探讨由连接蛋白43（Cx43）、细胞外基质金属蛋白酶诱导因子（EMMPRIN/CD147）、E-钙黏蛋白和波形蛋白组成的联合蛋白标志物系统，重点关注它们在OSCC侵袭性转移进展中的作用及其在预测预后方面的潜在应用价值。 方法：我们采用免疫组织化学分析方法，对24例OSCC患者的组织样本中Cx43、EMMPRIN、E-钙黏蛋白和波形蛋白的蛋白表达谱进行评估。通过不同感兴趣区域（ROIs）绘制转移过程图谱，包括邻近健康口腔黏膜（OM）、原发OSCC中心区、侵袭前沿（IF）及局部颈部淋巴结转移灶（LNM）。主要临床终点为无病生存期（DFS）和总生存期（OS）。 结果：在不同ROIs间观察到各标志物蛋白表达谱的显著变化（所有p值<0.05，具有统计学意义）。多变量Cox回归分析显示，EMMPRIN在侵袭前沿表达升高对DFS（p=0.019）和OS（p=0.023）具有显著影响。此外，联合预测分析表明该标志物系统对DFS（p=0.0017）和OS（p=0.00044）具有显著预测价值。 结论：该联合标志物系统展现出显著的预后预测能力。EMMPRIN在侵袭前沿表达升高显示出最强效应，可能成为具有潜力的新型抗转移治疗靶点。
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