Skip to main content
Top
Published in: Medical Oncology 2/2013

01-06-2013 | Original Paper

Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer

Authors: Yuan-zi Ye, Zhi-hong Zhang, Xiao-yun Fan, Xiao-lan Xu, Mei-li Chen, Bo-wen Chang, Yan-bei Zhang

Published in: Medical Oncology | Issue 2/2013

Login to get access

Abstract

Notch3 receptor is one of the mammalian Notch family receptors (Notch1–4) which plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis. Overexpression of Notch3 is associated with tumorigenesis. In order to assess the expression of Notch3 in Chinese non-small-cell lung cancer (NSCLC) patients and determine its association with prognosis, we designed a prospective study with five years of follow-up to evaluate Notch3 expression in NSCLC tissues and adjacent non-cancerous normal lung tissues from 131 patients undergoing surgical treatment by immunohistochemistry and western blot analysis. Notch3 had high expression in 67 of 131 cases of NSCLC (51.1 %), which was significantly higher than in adjacent noncancerous lung tissues. Moreover, Notch3 overexpression was significantly correlated with TNM stage (P = 5.41e−07 in squamous cell carcinoma, P = 5.338e−07 in adenocarcinoma) and lymph node metastasis (P = 0.00764 in squamous cell carcinoma, P = 0.01491 in adenocarcinoma). Kaplan–Meier survival analysis showed that the overall survival times in patients expressing Notch3 in NSCLC were shorter. Multivariate analysis further demonstrated that Notch3 was an independent prognostic factor for patients with NSCLC. Therefore, Notch3 might be a useful biomarker to predict the prognosis of patients with NSCLC.
Literature
1.
3.
go back to reference Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review 1975–2009 (vintage: populations). Bethesda: National Cancer Institute; 2009. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review 1975–2009 (vintage: populations). Bethesda: National Cancer Institute; 2009.
4.
go back to reference Sandler A, Gray R, Perry M, et al. Paclitaxel-carboplatin alone or with bevacizumab in non-small cell lung cancer. NEJM. 2006;355(24):2542–50.PubMedCrossRef Sandler A, Gray R, Perry M, et al. Paclitaxel-carboplatin alone or with bevacizumab in non-small cell lung cancer. NEJM. 2006;355(24):2542–50.PubMedCrossRef
5.
go back to reference Lee SY, Kim MJ, Jin G, et al. Choi somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers. J Thorac Oncol. 2010;5(11):1734–40.PubMedCrossRef Lee SY, Kim MJ, Jin G, et al. Choi somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers. J Thorac Oncol. 2010;5(11):1734–40.PubMedCrossRef
6.
go back to reference Casás-Selves M, Kim J, Zhang Z, et al. Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Res. 2012;72(16):4154–64.PubMedCrossRef Casás-Selves M, Kim J, Zhang Z, et al. Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Res. 2012;72(16):4154–64.PubMedCrossRef
8.
go back to reference Shawber CJ, Kitajewski J. Notch function in the vasculature: insights from zebrafish, mouse and man. BioEssays. 2004;26:225–34.PubMedCrossRef Shawber CJ, Kitajewski J. Notch function in the vasculature: insights from zebrafish, mouse and man. BioEssays. 2004;26:225–34.PubMedCrossRef
9.
10.
go back to reference Collins BJ, Kleeberger W, Ball DW. Notch in lung development and lung cancer. Semin Cancer Biol. 2004;14:357–64.PubMedCrossRef Collins BJ, Kleeberger W, Ball DW. Notch in lung development and lung cancer. Semin Cancer Biol. 2004;14:357–64.PubMedCrossRef
11.
go back to reference Lin L, Mernaugh R, Yi F, et al. Targeting specific regions of the Notch3 ligand-binding domain induces apoptosis and inhibits tumor growth in lung cancer. Cancer Res. 2010;70:632–8.PubMedCrossRef Lin L, Mernaugh R, Yi F, et al. Targeting specific regions of the Notch3 ligand-binding domain induces apoptosis and inhibits tumor growth in lung cancer. Cancer Res. 2010;70:632–8.PubMedCrossRef
12.
go back to reference Westhoff B, Colaluca IN, D’Ario G, et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 2009;106:22293–8.PubMedCrossRef Westhoff B, Colaluca IN, D’Ario G, et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 2009;106:22293–8.PubMedCrossRef
13.
go back to reference Baumgart A, Seidl S, Vlachou P, et al. ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 2010;70:5368–78.PubMedCrossRef Baumgart A, Seidl S, Vlachou P, et al. ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 2010;70:5368–78.PubMedCrossRef
14.
go back to reference Park JT, Chen X, Trope CG, et al. Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am J Pathol. 2010;177:1087–94.PubMedCrossRef Park JT, Chen X, Trope CG, et al. Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am J Pathol. 2010;177:1087–94.PubMedCrossRef
15.
go back to reference Rahman MT, Nakayama K, Rahman M, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol. 2012;138(4):535–44.PubMedCrossRef Rahman MT, Nakayama K, Rahman M, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol. 2012;138(4):535–44.PubMedCrossRef
16.
go back to reference Jonusiene V, Sasnauskiene A, Lachej N, et al. Down-regulated expression of Notch signaling molecules in human endometrial cancer. Med Oncol. 2013;30(1):438.PubMedCrossRef Jonusiene V, Sasnauskiene A, Lachej N, et al. Down-regulated expression of Notch signaling molecules in human endometrial cancer. Med Oncol. 2013;30(1):438.PubMedCrossRef
17.
go back to reference Yao J, Qian C. Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway. Med Oncol. 2010;27(3):1017–22.PubMedCrossRef Yao J, Qian C. Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway. Med Oncol. 2010;27(3):1017–22.PubMedCrossRef
18.
go back to reference Mann CD, Bastianpillai C, Neal CP, et al. Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma. PLoS ONE. 2012;7(12):e51119.PubMedCrossRef Mann CD, Bastianpillai C, Neal CP, et al. Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma. PLoS ONE. 2012;7(12):e51119.PubMedCrossRef
19.
go back to reference Kang H, An HJ, Song JY, et al. Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression. Histopathology. 2012;61:576–86.PubMed Kang H, An HJ, Song JY, et al. Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression. Histopathology. 2012;61:576–86.PubMed
20.
go back to reference Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136(1):260–71.PubMedCrossRef Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136(1):260–71.PubMedCrossRef
21.
go back to reference Mitsuhashi Y, Horiuchi A, Miyamoto T, et al. Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells. Histopathology. 2012;60(5):826–37.PubMedCrossRef Mitsuhashi Y, Horiuchi A, Miyamoto T, et al. Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells. Histopathology. 2012;60(5):826–37.PubMedCrossRef
22.
go back to reference Yeasmin S, Nakayama K, Rahman MT, et al. Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes. Gynecol Oncol. 2010;117:409–16.PubMedCrossRef Yeasmin S, Nakayama K, Rahman MT, et al. Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes. Gynecol Oncol. 2010;117:409–16.PubMedCrossRef
23.
go back to reference Ma D, Dong X, Zang S, et al. Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population. Asia Pac J Clin Oncol. 2011;7(4):385–91.PubMedCrossRef Ma D, Dong X, Zang S, et al. Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population. Asia Pac J Clin Oncol. 2011;7(4):385–91.PubMedCrossRef
24.
go back to reference Shah MM, Zerlin M, Li BY, et al. The role of notch and gamma-secretase inhibition in an ovarian cancer model. Anticancer Res. 2013;33(3):801–8.PubMed Shah MM, Zerlin M, Li BY, et al. The role of notch and gamma-secretase inhibition in an ovarian cancer model. Anticancer Res. 2013;33(3):801–8.PubMed
25.
go back to reference Chen X, Thiaville MM, Chen L, et al. Defining NOTCH3 target genes in ovarian cancer. Cancer Res. 2012;72(9):2294–303.PubMedCrossRef Chen X, Thiaville MM, Chen L, et al. Defining NOTCH3 target genes in ovarian cancer. Cancer Res. 2012;72(9):2294–303.PubMedCrossRef
Metadata
Title
Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer
Authors
Yuan-zi Ye
Zhi-hong Zhang
Xiao-yun Fan
Xiao-lan Xu
Mei-li Chen
Bo-wen Chang
Yan-bei Zhang
Publication date
01-06-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0595-7

Other articles of this Issue 2/2013

Medical Oncology 2/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine