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

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.

Notch signaling molecules as prognostic biomarkers for non-small cell lung cancer

“…Almost all cases of T cell acute lymphoblastic leukemia (T-ALL), and colorectal, pancreatic and ovarian cancer have been reported to exhibit aberrant Notch 3 expression (6,8,16,17). Our previous study also reported that Notch 3 overexpression was associated with a poor prognosis in NSCLC patients (18). However, the prognostic role of Notch 3 compared with other Notch family members and its association with Notch 1 in human NSCLC remains unclear.…”

Cigarette smoke induces the expression of Notch3, not Notch1, protein in lung adenocarcinoma

“…With respect to Notch3, Haruki et al (12) found that the positive expression rate was ~37% (32/87). However, Zhou et al (13) and Ye et al (14) identified that the level of Notch3 increased in NSCLC tissues. The deviations in the expression of Notch1 and Notch3 may be due to the heterogeneity of the lung cancer samples.…”

“…of LAC (9)(10)(11)(12)(13)(14). Therefore, the present study chose to analyze the expression of Notch1 and Notch3 proteins.…”

“…Haruki et al (12) reported that the positive expression rate of Notch3 was ~37% (32/87) in LAC and indicated that its mechanism of maintaining the neoplastic phenotype may proceed via the modulation of the epidermal growth factor pathway. Additional studies have revealed that the protein expression of Notch3 was higher in NSCLC tissues (13,14). Konishi et al (46) identified that the inhibition of Notch3 activation reduced the proliferation of A549 cells.…”

Notch and Wnt signaling pathway in cancer: Crucial role and potential therapeutic targets (Review)

“…Zhou et al (68) detected Notch 3 receptor expression in different types of lung cancer, and they found that Notch 3 expression was high in lung squamous cell carcinoma and adenocarcinoma, but low in small cell carcinoma, compared with the corresponding non-tumor tissue. In addition, the Notch 3 receptor showed its potential ability of predicting the prognosis of patients with NSCLC (69). In this recent report, high levels of the Notch 3 receptor were detected in ~51.1% of cases and were associated with a short survival rate.…”