Pyk2 level is a novel prognostic marker for patients with esophageal squamous cell carcinoma after radical surgery

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in East Asia. Surgical resection is currently the typical treatment. However, due to the highly invasive and metastatic characteristic of the disease, the mortality rate is still high. A search for potential prognostic biomarkers and therapeutic targets is very necessary. Here, we studied the expression of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine protein kinase, in ESCC and its influence on prognosis. A total of 112 cases of ESCC and paired adjacent normal tissues (NT) were organized in tissue microarray (TMA) from the Nantong First People's Hospital. Our analysis of TMA revealed that Pyk2 levels were higher in ESCC than in paired adjacent NT by immunohistochemistry (p<0.001). Western blot and real-time quantitative PCR analysis (p=0.0359) also reached similar conclusions. To further explore the significance of Pyk2 in ESCC, another set of tissue microarrays was collected from the Affiliated Hospital of Nantong University, which includes 241 consecutive patients undergoing radical surgery for ESCC, to perform IHC scores. We demonstrated that the expression level of Pyk2 was positively correlated with N stage (node negative versus node positive, p=0.02) and clinical stage (I + II versus III + IV, p=0.042). Univariate and multivariate analyses suggested that high Pyk2 expression was an independent prognostic factor for overall survival with ESCC. Cell function studies found that Pyk2 promoted tumor proliferation and migration and reduced apoptosis. Pyk2 knockdown enhanced the sensitivity to cisplatin in ESCC cells. Western blot analysis confirmed that Pyk2 may promote tumor progression by activating the Akt signaling pathway.