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Updated: Jun 10, 2026

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
[Expression and its Clinical Significance of NOK, EGFR in NSCLC.]
Zhipei Zhang1, Tao Jiang, Yingchun Deng
1Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Background:
NOK (Novel Oncogene with Kinase-domain) is a newly identified receptor protein-tyrosine kinases (RPTKs) subfamily, which possesses strong oncogenic potential including enhancing cell transformation, tumorigenesis, invasion and metastasis. However, NOK protein lacks extracellular domain, and how the NOK is activated by the membrane receptor and the expression of NOK in non small cell lung cancer (NSCLC) are not clear. Our aim of this study was to investigate the expressions of NOK, EGFR proteins in NSCLC.
Methods:
The expression rates of NOK, EGFR proteins in 155 cases with NSCLC was deteced by immunohistochemical stain; The clinical correlations between two proteins were analyzed by statistics.
Results:
The NOK positive expression was mainly located in cytoplasm and EGFR was mainly located in the plasma membrane and cytoplasm. NOK, EGFR proteins were high expressed in NSCLC and there were extremely differences comparing the expression of NOK, EGFR proteins in squamous cell lung cancer, lung adenocarcinoma with those in corresponding normal tissue respectively (P<0.001); and there were no significant differences between the two kinds of the cancers for their comparison of NOK, EGFR expression (P=0.099; P=0.23); however, there were significant differences for NOK and EGFR expression among histological grades and TNM stages in squamous cell lung cancers, lung adenocarcinoma (P<0.01). There were correlation between positive and intensity of NOK and EGFR expression in whatever total NSCLC or squamous cell lung cancer or lung adenocarcinoma (P<0.001), while the correlation coefficients(rs) were 0742, 0.722, 0.756 respectively.
Conclusions:
The NOK proteins are highly expressed in the NSCLC, and the expression rates of NOK proteins are correlated with the cancers' histological grades and TNM stages, which may be concern with tumorgenesis and progression; the positive expression rate and intensity of NOK protein correlate well with the expression of EGFR protein in NSCLC, which the activation of NOK probably owe to EGFR activation, all that would provide evidence for further study on the effective mechanism of NOK in the tumorigenesis or tumor progression.
Insights
Novel Oncogene with Kinase-domain (NOK) proteins are highly expressed in non-small cell lung cancer (NSCLC) and correlate with tumor progression. NOK expression is linked to Epidermal Growth Factor Receptor (EGFR) activation, suggesting a role in lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Context:
- Novel Oncogene with Kinase-domain (NOK) is a receptor protein-tyrosine kinases (RPTKs) subfamily with oncogenic potential.
- The activation mechanism of NOK and its expression in non-small cell lung cancer (NSCLC) remain unclear.
- NOK lacks an extracellular domain, necessitating investigation into its activation by membrane receptors.
Purpose:
- To investigate the expression of NOK and Epidermal Growth Factor Receptor (EGFR) proteins in NSCLC.
- To analyze the clinical correlations between NOK and EGFR expression in NSCLC patients.
Summary:
- Immunohistochemical staining in 155 NSCLC cases revealed high expression of both NOK and EGFR proteins.
- NOK and EGFR expression levels significantly differed in NSCLC compared to normal tissues (P<0.001).
- Expression of NOK and EGFR correlated with histological grades and TNM stages in squamous cell lung cancer and lung adenocarcinoma (P<0.01).
- A strong correlation was observed between NOK and EGFR expression intensity and positivity (rs=0.742-0.756, P<0.001).
Impact:
- High NOK expression in NSCLC correlates with tumor grade and stage, suggesting involvement in tumorigenesis and progression.
- The correlation between NOK and EGFR expression implies EGFR activation may trigger NOK activation.
- Findings provide a basis for further research into NOK's mechanism in lung cancer development and progression.
- This study highlights potential therapeutic targets for NSCLC.
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