Predictive value of protease-activated receptor-2 (PAR2 ) in cervical cancer metastasis.

ABSTRACT

Metastasis is the primary cause of an unfavourable prognosis in patients with malignant cancer. Over the last decade, the role of proteinases in the tumour microenvironment has attracted increasing attention. As a sensor of proteinases, proteinase-activated receptor 2 (PAR2 ) plays crucial roles in the metastatic progression of cervical cancer. In the present study, the expression of PAR2 in multiple types of cancer was analysed by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier plotter was used to calculate the correlation between survival and the levels of PAR2 , Grb-associated binding protein 2(Gab2) and miR-125b. Immunohistochemistry (IHC) was performed to examine PAR2 expression in a tissue microarray (TMA) of CESCs. Empower Stats was used to assess the predictive value of PAR2 in the metastatic potential of CESC. We found that PAR2 up-regulation was observed in multiple types of cancer. Moreover, PAR2 expression was positively correlated with the clinicopathologic characteristics of CESC. miR-125b and its target Gab2, which are strongly associated with PAR2 -induced cell migration, are well-characterized as predictors of the prognostic value of CESC. Most importantly, the Cancer Genome Atlas (TCGA) data set analysis showed that the area under the curve (AUC) of the PAR2 model was significantly greater than that of the traditional model (0.833 vs 0.790, P < .05), demonstrating the predictive value of PAR2 in CESC metastasis. Our results suggest that PAR2 may serve as a prognostic factor for metastasis in CESC patients.