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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Diagnostic relevance of overexpressed NOK mRNA in breast cancer
Ryosuke Moriai1, Daisuke Kobayashi, Tomoko Amachika
1Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Abstract:
A novel oncogene with a kinase domain (NOK), a receptor protein tyrosine kinase, has been reported to cause proliferation of normal cells, suggesting its possible use as a diagnostic marker in human cancer. To determine the significance of NOK expression in cancer cells, the effect of NOK inhibition was first examined on cell proliferation in vitro. The degree of expression in 52 clinical breast cancer samples was then correlated with clinical features. The transduction of NOK small inhibitory (si) RNA in T47D breast cancer cells decreased NOK mRNA expression, thereby inhibiting growth. When the mean expression in non-cancerous tissues from the same breast resection specimens +/-2SD was used as a cut-off value, 67.3% of breast cancers were positive for NOK expression - a higher positivity rate than that found for c-erbB2 (28.8%). NOK mRNA expression did not correlate with c-erbB2 expression, indicating the independence of NOK as a diagnostic marker. Furthermore, NOK mRNA was highly expressed even at early clinical stages. NOK mRNA might be an ideal target to support the diagnosis of breast cancer especially in tiny tumors in which the malignancy cannot be confirmed by other means.
Insights
A novel oncogene with a kinase domain (NOK) shows high expression in breast cancer, acting as a potential diagnostic marker. Inhibiting NOK suppressed cancer cell growth, highlighting its role in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- A novel oncogene with a kinase domain (NOK), a receptor protein tyrosine kinase, promotes normal cell proliferation.
- Its potential as a diagnostic marker in human cancers warrants investigation.
Purpose of the Study:
- To determine the significance of NOK expression in cancer cells.
- To evaluate NOK as a diagnostic marker for breast cancer.
- To assess the therapeutic potential of NOK inhibition.
Main Methods:
- NOK small inhibitory (si) RNA was used to inhibit NOK mRNA expression in T47D breast cancer cells.
- Breast cancer cell proliferation was assessed in vitro.
- NOK mRNA expression levels were correlated with clinical features in 52 breast cancer samples.
Main Results:
- NOK inhibition via siRNA decreased NOK mRNA expression and inhibited cancer cell growth.
- 67.3% of breast cancers showed positive NOK expression, exceeding the rate for c-erbB2 (28.8%).
- NOK mRNA expression was independent of c-erbB2 and detected even in early clinical stages.
Conclusions:
- NOK mRNA is a promising diagnostic marker for breast cancer, particularly for small tumors.
- NOK inhibition demonstrates therapeutic potential.
- NOK mRNA expression is a valuable biomarker, independent of c-erbB2.