Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
J Oral Pathol Med. 2018 Feb;47(2):121-127. doi: 10.1111/jop.12651. Epub 2017 Nov 7.
Rho-associated coiled-coil kinase 2 (ROCK2) is an oncoprotein that controls cytoskeleton organization and acts as prognostic marker in different types of solid tumors. ROCK2 overexpression is also observed in cancer-associated fibroblasts (CAF), which suggests its relevance within the tumor microenvironment. This study aimed to access the prognostic value of ROCK2 in oral squamous cell carcinomas (OSCCs) and its association with CAF density.
Rho-associated coiled-coil kinase 2 immunohistochemical analysis was applied in 93 OSCC samples from 2 centers in Brazil and Finland. The samples were also stained for isoform α of smooth muscle actin (α-SMA) to characterize the presence of CAF in the tumor stroma. Clinicopathological associations were analyzed using Chi-squared test, survival curves were constructed according to the Kaplan-Meier method, and Cox proportional hazard model was applied for multivariate survival analysis.
Advanced clinical stage (P = .002) and increased density of CAF (P = .002) were significantly associated with high ROCK2 expression. The high expression of ROCK2 was also associated with shortened disease-specific survival (HR: 2.22, 95% CI: 1.15-4.38, P = .04), but the association did not withstand the Cox multivariate survival analysis.
The findings suggest that high ROCK2 expression in OSCC is associated with advanced disease and follows the increase in CAF density, which may be important for tumor progression.
Rho 相关卷曲螺旋激酶 2（ROCK2）是一种癌蛋白，可控制细胞骨架的组织，并且作为不同类型实体瘤的预后标志物。ROCK2 的过表达也在癌相关成纤维细胞（CAF）中观察到，这表明其在肿瘤微环境中的相关性。本研究旨在评估 ROCK2 在口腔鳞状细胞癌（OSCC）中的预后价值及其与 CAF 密度的关联。
在来自巴西和芬兰的 2 个中心的 93 例 OSCC 样本中应用 Rho 相关卷曲螺旋激酶 2 免疫组织化学分析。还对平滑肌肌动蛋白同工型 α（α-SMA）进行染色，以表征肿瘤基质中 CAF 的存在。使用卡方检验分析临床病理关联，根据 Kaplan-Meier 方法构建生存曲线，并应用 Cox 比例风险模型进行多变量生存分析。
临床分期较晚（P =.002）和 CAF 密度增加（P =.002）与 ROCK2 高表达显著相关。ROCK2 的高表达也与疾病特异性生存时间缩短相关（HR：2.22，95%CI：1.15-4.38，P =.04），但 Cox 多变量生存分析并未证实这一关联。
这些发现表明，OSCC 中 ROCK2 的高表达与疾病进展相关，并且随着 CAF 密度的增加而增加，这对于肿瘤进展可能很重要。
