Notch1 phenotype and clinical stage progression in non-small cell lung cancer

Journal of Hematology & Oncology

Sherry X Yang¹  James H Doroshow²  Percy Ivy⁴  Joseph E Tomaszewski²  Lucio Miele³  Naoko Takebe⁴  Larry Rubinstein⁵  Dat Nguyen¹ 

[1] National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA;Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA;Stanley Scott Cancer Center, Louisiana State University Health Sciences Center and Louisiana Cancer Research Consortium, New Orleans, LA, USA;Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA;Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA

关键词: Stage;    NSCLC;    Notch1;    N1-ICD;    Lung cancer;   

Others  :  1133371
DOI  :  10.1186/s13045-014-0104-2

 received in 2014-09-26, accepted in 2014-12-30,  发布年份 2015

【 摘 要 】

Background

Notch1 transmembrane receptor is activated through ligand-binding- triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC.

Methods

Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided.

Results

Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 – 63%). It was negatively associated with stage (r = - 0.43, P < 0.001) and nodal status (r = - 0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells.

Conclusions

Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis.

【 授权许可】

   
2015 Nguyen et al.; licensee Biomed Central.

【 图 表 】

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