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

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Abstract

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.

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Data availability

Data of this study is available from the corresponding author on reasonable request.

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Funding

The study was supported by a scientific research project of the Nantong Municipal Health Committee (MB2020016).

Author information

Authors and Affiliations

  1. Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China

    Tong Zhu & Guoxin Mao

  2. Department of Oncology, The First People’s Hospital of Yancheng, Yancheng, China

    Tong Zhu

  3. Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong, China

    Qiuxing Yang & Jingjing Shao

  4. Department of Pathology, Tumor Hospital Affiliated to Nantong University, Nantong, China

    Zhuolin Chen

  5. Nantong Center for Disease Control and Prevention Institute of Chronic Noncommunicable Diseases Prevention and Control, Nantong, China

    Bo Cai

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  1. Tong Zhu
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Contributions

All authors have read the final manuscript and agreed to publish. G.M and Q.Y designed experiment ideas and provided funds. B.C followed up patient’s survival status. T.Z conducted experimental operations and statistical analysis and wrote articles. J.S and Z.C assisted in drawing and carefully reviewing manuscripts.

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Correspondence to Bo Cai or Guoxin Mao.

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Tong Zhu and Qiuxing Yang are co-first authors of this article.

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Supplementary Figure 1

Pyk2 knockdown enhanced cisplatin sensitivity in ESCC. a-b KYSE150 and ECA109 cell lines were treated different concentrations of cisplatin for 48h. Then, the cell viability was examined by CCK8 assay. c KYSE150 siR-Pyk2 and siR-NC cells were treated with cisplatin (4ug/mL). d ECA109 siR-Pyk2 and siR-NC cells were treated with cisplatin (1ug/mL). *p < 0.05 (n=3). (PNG 208 kb)

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Zhu, T., Yang, Q., Shao, J. et al. Pyk2 level is a novel prognostic marker for patients with esophageal squamous cell carcinoma after radical surgery. Virchows Arch 479, 905–917 (2021). https://doi.org/10.1007/s00428-021-03153-y

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  • DOI: https://doi.org/10.1007/s00428-021-03153-y

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