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Updated: Jan 20, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
The prognostic significance of SHP2 and its binding protein Hook1 in non-small cell lung cancer
Lingjuan He1, Yinyan Li1, Xin Huang1
1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, People's Republic of China.
Background:
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.
Insights
High SHP2 protein expression correlates with poor prognosis in non-small cell lung cancer (NSCLC). This study analyzed SHP2 and Hook1 expression, finding SHP2 is an independent prognostic factor for overall survival in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Previous research indicated Hook1 inhibits SHP2 phosphatase activity in epithelial-mesenchymal transition (EMT) regulation within lung cancer.
- This study comprehensively analyzes SHP2 and Hook1 expression and their prognostic implications in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the expression patterns of SHP2 and Hook1 in NSCLC.
- To determine the relationship between SHP2 and Hook1 expression and patient prognosis in NSCLC.
Main Methods:
- Immunohistochemistry and Western blot analysis were used to assess SHP2 and Hook1 expression in 121 NSCLC patients.
- Overall survival rates were analyzed using Cox's hazard ratio multivariate analysis and the log-rank test.
Main Results:
- SHP2 protein expression was observed in 58.4% of NSCLC tumor specimens.
- A significant correlation was found between SHP2 and Hook1 expression. Hook1 was downregulated, and SHP2 showed a non-significant tendency to overexpress in NSCLC compared to normal lung tissue.
- Low SHP2 expression was associated with significantly better overall survival (median 40 vs 24 months, p=0.004), and SHP2 expression level was identified as an independent prognostic factor for overall survival.
Conclusions:
- SHP2 plays a significant role in NSCLC development and progression.
- SHP2 has potential as a clinical biomarker for NSCLC prognosis.
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