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 (OSCCs) and its association with CAF density. METHODS: 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. RESULTS: 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. 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.
Subject(s)
Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/enzymology , Mouth Neoplasms/pathology , rho-Associated Kinases/metabolism , Actins/metabolism , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Biomarkers, Tumor/analysis , Brazil , Cancer-Associated Fibroblasts/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Female , Finland , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/surgery , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Risk Factors , Smoking , Survival Analysis , Tumor MicroenvironmentABSTRACT
OBJECTIVES: Elderly individuals with Candida-related denture stomatitis (DS) present with a reduced defence against Candida albicans. This study evaluated levels of antimicrobial mediators in the elderly DS saliva and salivary neutrophils' activation characteristics compared with elderly and young without DS. METHODS: Salivary peroxidases (SPO) and elastase activities (ELA), nitric oxide (NO), transforming growth factor beta (TGF-ß), IL-6 and CCL3 production were determined in saliva from elderly with or without DS, and young control individuals. TLR4, CXCR1, CD11b, CD16 and CD32 expression on salivary neutrophils were evaluated. Correlations between number and apoptosis rate of salivary neutrophils, enzymatic activities and cytokine levels were determined. RESULTS: Elderly DS individuals exhibited the lowest SPO and ELA activities. Also, the activity of both enzymes was low in elderly without DS. Although both elderly groups showed higher salivary NO and TGF-ß levels compared to young control groups, elderly DS presented the highest salivary NO, TGF-ß, IL-6 and CCL3 levels. Decreased percentages of salivary TLR4(+) and CD16(+) neutrophils were detected in both elderly groups. Although these damages could influence the establishment and persistence of DS, the highest levels of salivary IL-6 and CCL3 in elderly DS could be preventing more serious complications.
