Khromov Tatjana, Fischer Lucas, Leha Andreas, Bremmer Felix, Fischer Andreas, Schliephake Henning, Rahat Michal Amit, Brockmeyer Phillipp
Department of Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, Germany.
Department of Urology, University Medical Center Goettingen, 37075 Goettingen, Germany.
Cancers (Basel). 2023 Oct 10;15(20):4924. doi: 10.3390/cancers15204924.
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.
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).
Substantial changes in the expression profiles of the different marker proteins were observed among the different ROIs, with all -values < 0.05, signifying statistical significance. Multivariable Cox regression analysis results showed a significant effect of increased EMMPRIN expression toward the IF on DFS ( = 0.019) and OS ( = 0.023). Furthermore, the combined predictive analysis showed a significant predictive value of the marker system for DFS ( = 0.0017) and OS ( = 0.00044).
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.
转移性口腔鳞状细胞癌（OSCC）与患者预后不良相关。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）过程导致的变化，以及与肿瘤微环境（TME）的相互作用。在本研究中，我们研究了由连接蛋白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预测预后的潜在效用。
我们进行了免疫组织化学分析，以评估使用从24例OSCC患者获得的组织样本中Cx43、EMMPRIN、E-钙黏蛋白和波形蛋白的蛋白表达谱。通过不同的感兴趣区域（ROI）绘制转移过程，包括相邻健康口腔黏膜（OM）、原发性OSCC中心、侵袭前沿（IF）和局部颈部淋巴结转移（LNM）。主要临床终点为无病生存期（DFS）和总生存期（OS）。
在不同的ROI中观察到不同标志物蛋白表达谱的显著变化，所有P值<0.05，表明具有统计学意义。多变量Cox回归分析结果显示，IF处EMMPRIN表达增加对DFS（P = 0.019）和OS（P = 0.023）有显著影响。此外，联合预测分析显示该标志物系统对DFS（P = 0.0017）和OS（P = 0.00044）具有显著预测价值。
联合标志物系统具有显著的预测患者预后的能力。IF处EMMPRIN表达增加显示出最强的影响，可能是一种有趣的新型抗转移治疗方法。
