Significance of PYK2 level as a prognosis predictor in patients with colon adenocarcinoma after surgical resection

Abstract

Background: Proline-rich/Ca2+-activated tyrosine kinase 2 (PYK2) belongs to the non-receptor tyrosine kinase family, regulates downstream signaling via catalyzing protein phosphorylation. We aimed to investigate clinical significance and mechanisms of PYK2 in colon adenocarcinoma (CAC). Methods: Real time quantitative PCR and immunohistochemistry staining was used to evaluate the expression of PYK2 in clinical CAC tissues. Its association with clinicopathologic characteristics was analyzed by Chi-square test. Kaplan-Meier univariate survival analysis and multivariate Cox regression analysis were used to identify clinical significance of PYK2 in the overall survival of CAC patients. Transfection of PYK2 were conducted to reveal the underlying mechanism in regulating CAC progression. Results: We found that PYK2 was upregulated in CAC tissues compared with normal colon tissues on both RNA and protein levels. Higher tissue PYK2 expression level was closely associated with lymph node metastasis. Statistical analyses indicated PYK2 as an independent prognostic biomarker for CAC. Cellular studies demonstrated that PYK2 enhanced the capacities of tumor proliferation and invasion. Moreover, the phosphorylation level of AKT was positively correlated with PYK2 expression, subsequently modulate expression of c-Myc and Cyclin D1, suggesting that PYK2 may promote tumor progression through activating AKT signaling. Conclusion: High PYK2 in CAC tissues indicate poor prognosis.