Clinicopathologic significance of ROCK2 expression in oral squamous cell carcinomas

Abstract

Background

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 (OSCC) and its association with CAF density.

Methods

ROCK2 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. Clinicopathologic associations were analyzed using chi-square test, survival curves were constructed according to the Kaplan-Meier method, and Cox proportional hazard model was applied for multivariate survival analysis.

Results

Advanced clinical stage (p=0.002) and increased density of CAF (p=0.002) 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=0.04), but the association did not withstand the Cox multivariate survival analysis.

Conclusions

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.

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