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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.
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OBJECTIVE@#This study aimed to investigate the expression and clinical significance of proline-rich tyrosine kinase 2 (Pyk2) and phospho-protein kinase B (p-AKT) in tongue squamous cell carcinoma (TSCC) and adjacent nontumor tissues.@*METHODS@#The Pyk2 and p-AKT protein levels were detected via immunohistochemistry in 45 cases of TSCC tissues and 30 cases of adjacent nontumor tissues. The relationships of the two protein levels and clinicopathological characteristics were also analyzed.@*RESULTS@#Pyk2 and p-AKT levels were significantly higher in the TSCC tissues than in the adjacent nontumor tissues (P<0.05). Nontumor tissues showed poor or no expression. The expression levels of the two proteins were positively correlated (γs=0.412). The expression of Pyk2 was associated with histopathological differentiation type, regional lymph node metastasis, and TNM staging (P<0.05), but not with age and gender. The expression of p-AKT was only related to histopathological differentiation types (P<0.05).@*CONCLUSIONS@#The abnormal expression of Pyk2 and p-AKT proteins might be closely related to the development and progression of TSCC. Joint detection can be used as an indicator to estimate the degree of TSCC.
Subject(s)
Humans , Carcinoma, Squamous Cell , Metabolism , Focal Adhesion Kinase 2 , Metabolism , Prognosis , Proto-Oncogene Proteins c-akt , Metabolism , Tongue Neoplasms , MetabolismABSTRACT
Objective To investigate the influence of proline-rich tyrosine kinase 2 (Pyk2)gene RNA interference on proliferation,invasion and migration of Hep3B hepatocellular carcinoma cells.Methods The Pyk2 gene RNA interference vector was transfected in Hep3B hepatocellular carcinoma cells by lipofectamine. The Hep3B cells divided into three groups:siRNA group (the vector with Pyk2 RNAi gene was transfected), negative control group (the vector without Pyk2 RNAi gene was transfected),and blank control group (no vectors was transfected).Pyk2 mRNA and protein were detected using reverse transcription reverse transcription-poly-merase chain reaction (RT-PCR)and Western blotting.The biological behavior including cell proliferation,inva-sion and migration were detected by 3-(4,5-dimethyl-2-thiazoly)-2,5-diphenyl-2H-tetrazolium bromide (MTT), transwell and wound healing assay,respectively.Results The expression of Pyk2 mRNA of Hep3B cell line in siRNA group (0.1 6 ±0.03)was significantly decreased than those in negative group (0.74 ±0.1 3)and blank control group (0.77 ±0.1 6),with statistically significant differences (t=51 .46,P=0.000;t=53.21 ,P=0.000).The expression of Pyk2 protein of Hep3B cell line in siRNA group (0.24 ±0.06)was significantly decreased than those in negative group (0.83 ±0.05)and blank control group (0.91 ±0.06),with statisti-cally significant differences (t=57.29,P=0.000;t=68.53,P=0.000).The cell proliferation inhibition rate at 48 hours in siRNA group (26.1 7%±0.28%)was significantly raised than those in negative group (9.28%± 0.22%)and blank control group (6.47%±0.31%),with statistically significant differences (t=31 .45,P=0.004;t=34.64,P=0.002).The number of transmembrane cells in siRNA group (32.5 ±8.5)/1 0 HP was significantly declined than those in negative group (98.4 ±1 2.3 )/1 0 HP and blank control group (1 1 2.6 ± 1 1 .3)/1 0 HP,with statistically significant differences (t=95.64,P=0.000;t=1 05.1 7,P=0.000).The wound healing assay in siRNA group (28.1 7%±1 .46%)was significantly lower than those in negative group (77.38%±2.24%)and blank control group (79.41%±3.1 7%),with statistically significant (t=85.86,P=0.000;t=89.37,P=0.000).Conclusion Pyk2 gene involves the proliferation,invasion and migration of Hep3B cells,which has close correction with development and metastasis of hepatocellular carcinoma.Pyk2 gene is very helpful to become a molecular target for the diagnosis and treatment of hepatocellular carcinoma.
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Backgroud and Objective Proline-rich tyrosine kinase2(Pyk2) is a Ca~(2+) sensitive,non-receptor tyrosine protein kinase.Previous reports showed Pyk2 involved in development of left ventrieular hypertrophy. The present paper aimed to study the effects of valsartan on ventricular hypertrophy and its effect on the expression of Pyk2 in myocardium in renovascular hypertensive rats(RHR).Methods Two-kidney and one-clip(2K1C) renal hypertensive model was established in Sprague-Dawley rats by chronic partial occlusion of left renal artery,and ran- domized to receive valsartan (30 mg/kg?d) or without treatment for 4 or 8 weeks.Left ventricular mass to body mass ratio was measured.Pyk2 protein expression and phosphorylation was detected by Western blotting.Results Blood pressure,left ventricular mass to body mass ratio,Pyk2 activity in myocardium of RHR were increased gradu- ally.Valsartan reduced BP and prevent myocardial hypertrophy(P