OncoTargets and Therapy (Jul 2019)

The prognostic significance of SHP2 and its binding protein Hook1 in non-small cell lung cancer

  • He L,
  • Li Y,
  • Huang X,
  • Cheng H,
  • Ke Y,
  • Wang L

Journal volume & issue
Vol. Volume 12
pp. 5897 – 5906

Abstract

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Lingjuan He,1 Yinyan Li,1 Xin Huang,1 Hongqiang Cheng,2 Yuehai Ke,2 Linrun Wang11Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, People’s Republic of China; 2Department of Pathology and Pathophysiology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou 310058, People’s Republic of ChinaBackground: We previously reported that Hook1 inhibits the phosphatase activity of SHP2 in the regulation of the epithelial-mesenchymal transition (EMT) in lung cancer. In this study, we performed a comprehensive analysis of SHP2 and Hook1 expression and relationships with the prognosis of patients with non-small cell lung cancer (NSCLC).Materials and methods: A total of 121 patients with NSCLC were included in this study. Expression of SHP2 and Hook1 was assessed by immunohistochemistry and Western blot analysis. The overall survival rate of NSCLC patients was analysed using Cox’s ratio hazard multivariate analysis and the log-rank test.Results: In tumour tissue specimens, positive expression rates of SHP2 proteins were 58.4% by immunohistochemical analysis. A significant correlation between expression of SHP2 and that of Hook1 was observed. Based on Western blot analysis, we found that Hook1 was downregulated and that SHP2 has a tendency to overexpress without statistical significance in NSCLC tissues compared with their levels in normal lung tissues. The median overall survival (OS) of NSCLC patients who presented low levels of SHP2 expression were better (40 vs 24 months, p=0.004) than those of patients who exhibited high levels of SHP2 expression. The results of multivariate analysis showed that the level of SHP2 expression was an independent prognostic factor for OS.Conclusion: SHP2 might play an important role in NSCLC and has the potential to serve as a clinical biomarker or NSCLC.Keywords: SHP2, Hook1, non-small cell lung cancer (NSCLC), protein expression

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