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Pyk2 level is a novel prognostic marker for patients with esophageal squamous cell carcinoma after radical surgery
Virchows Archiv ( IF 3.5 ) Pub Date : 2021-07-27 , DOI: 10.1007/s00428-021-03153-y
Tong Zhu 1, 2 , Qiuxing Yang 3 , Jingjing Shao 3 , Zhuolin Chen 4 , Bo Cai 5 , Guoxin Mao 1
Affiliation  

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.



中文翻译:

Pyk2水平是食管鳞癌根治术后新的预后标志物

食管鳞状细胞癌(ESCC)是东亚地区最常见的恶性肿瘤之一。手术切除是目前典型的治疗方法。但由于该病的侵袭性和转移性强,病死率仍然很高。寻找潜在的预后生物标志物和治疗靶点是非常必要的。在这里,我们研究了富含脯氨酸的酪氨酸激酶 2 (Pyk2),一种非受体酪氨酸蛋白激酶,在 ESCC 中的表达及其对预后的影响。在南通市第一人民医院的组织微阵列(TMA)中组织了总共 112 例 ESCC 和配对的相邻正常组织(NT)。我们对 TMA 的分析表明,通过免疫组织化学发现,ESCC 中 Pyk2 水平高于配对相邻 NT(p<0.001)。蛋白质印迹和实时定量 PCR 分析 ( p = 0.0359) 也得出了类似的结论。为了进一步探讨 Pyk2 在 ESCC 中的意义,从南通大学附属医院收集了另一组组织微阵列,其中包括 241 名接受 ESCC 根治性手术的连续患者,以进行 IHC 评分。我们证明 Pyk2 的表达水平与 N 分期(淋巴结阴性与淋巴结阳性,p = 0.02)和临床分期(I + II 与 III + IV,p=0.042)。单变量和多变量分析表明,高 Pyk2 表达是 ESCC 总生存率的独立预后因素。细胞功能研究发现Pyk2促进肿瘤增殖和迁移并减少细胞凋亡。Pyk2 敲低增强了 ESCC 细胞对顺铂的敏感性。蛋白质印迹分析证实 Pyk2 可能通过激活 Akt 信号通路促进肿瘤进展。

更新日期:2021-07-27
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