Pyk2 expression in non-muscle invasive bladder cancer and its clinical significance

Abstract

Objective To investigate the expression of proline rich tyrosine kinase 2(Pyk2) in non-muscle invasive bladder cancer , and analyze its correlation to clinicopathologic features and prognosis of non-muscle invasive bladder cancer. Methods 114 surgical specimens and 50 normal bladder mucosa specimens were collected from 114 non-muscle invasive bladder cancer patients who underwent TURBT at our hospital, from June 2013 to March 2018.Of the 114 patients, 63 were male and 51 were female, aged 42-87 years, average age of (63.6±13.8) years, 73 cases of tumor <3 cm, 41 cases of tumor ≥3 cm, 83 cases were single and 31 cases were multiple tumor, 53 cases were high grade and 61 cases were low grade, 59 cases were Ta and 55 cases were T1 stage.Pyk2 protein expression was detected by immunohistochemistry and western blot. The correlation of the expression of Pyk2 with clinicopathologic features, including gender, age, tumor size, the number of tumors, histological grade and clinical stage were analyzed. Survival analysis was calculated by using the Kaplan-Meier method, and the difference in survival curve was analyzed by using the log-rank test. Association of Pyk2 expression with prognosis of non-muscle invasive bladder cancer analyzed by using the Cox proportional hazards regression model. Results Compared with normal bladder tissues, expression of Pyk2 protein was increased in bladder cancer tissue significantly(0.571±0.230 vs. 0.253±0.152, P<0.01). The expression of Pyk2 protein was closely related to clinical stage(P=0.027) and grade(P=0.010), rather than gender(P=0.275), age(P=0.419), tumor size (P=0.317), and tumor number(P=0.208). The recurrence rate in the Pyk2 positive group and negative group were 46.1%(35/76)and 28.9%(11/38)respectively. The progression rate in the Pyk2 positive group and negative group were 35.5%(27/76)and 10.5%(4/38)respectively. Survival analysis suggested expression of Pyk2 in non-muscle invasive bladder cancer had a significant relation to recurrence-free survival rate(P<0.001) and progression-free survival rate(P=0.003). In the multivariable Cox analysis, we found that Pyk2 protein was an independent predictor of recurrence-free survival rate(HR 0.245, 95%CI 0.078-0.768, P=0.016) and progression-free survival rate(HR 0.095, 95%CI 0.012-0.764, P=0.027). Conclusions The expression of Pyk2 in non-muscle invasive bladder cancer was significantly increased. The expression of Pyk2 has a significant relation to recurrence and progression of non-muscle invasive bladder cancer. High Pyk2 expression is an independent prognostic factor in non-muscle invasive bladder cancer. Key words: Proline rich tyrosine kinase 2; Non-muscle invasive bladder cancer; Prognosis