Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma

Abstract

BackgroundAccording to the International Multidisciplinary Classification of Lung Adenocarcinoma (LAD) by International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) in 2011, the diagnosis of LAD is changing from simple morphology into a comprehensive multidisciplinary classification. The aim of this study is to detect the expression of Notch-1 and analyze its clinicopathological or prognostic significance in different histological subtypes of Lung Adenocarcinomas (LADs).MethodsWestern blot and Semi-quantitative Reverse transcription-polymerase chain reaction (RT-PCR) assays, as well as immunohisitochemistry, were performed to detect the expression of Notch-1 in LAD cells and tissue samples. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the correlation of Notch-1 expression with clinicopathological factors and prognosis of LAD patients.ResultsThe expression level of Notch-1 protein in LAD cell lines or tissues was significantly lower than that in normal human bronchial epithelial cell line (16HBE) or nontumor tissues (P < 0.05). By statistical analyses, it was observed that negative Notch-1 expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.026) in LAD patients. Also, the recurrence rate of Notch-1-positive group was higher than the Notch-1-negative group (P = 0.001), and patients with positive Notch-1 expression have a prolonged progression of overall survival (P = 0.033). More interestingly, the expression of Notch-1 protein was often observed to be negative in solid predominant adenocarcinoma (SPA) tissues, but highly expressed in papillary predominant adenocarcinoma (PPA) and micropapillary predominant adenocarcinoma (MPA) tissues. Kaplan-Meier survival analysis showed that patients with positive Notch-1 expression had a prolonged progression of overall survival compared with those with negative Notch-1 expression (P = 0.033). The median survival time of Notch-1-positive or negative patients was 64.6 months (95% CI: 31.497-97.703 months) or 36.0 months (95% CI: 12.132-59.868 months).ConclusionsNotch-1 could be used as a predictable biomarker to be detected in different pathological and histological subtypes in LAD for diagnosis or prognosis.

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

“…By contrast, a study by Huang et al (11), which focused on LAC, demonstrated opposing results. With respect to Notch3, Haruki et al (12) found that the positive expression rate was ~37% (32/87).…”

“…Certain studies (9)(10)(11) have produced controversial findings concerning the expression of Notch1 protein in NSCLC; Donnem et al (9) and Jiang et al (10) concluded that the overexpression of Notch1 was associated with a poorer prognosis in patients with NSCLC. By contrast, a study by Huang et al (11), which focused on LAC, demonstrated opposing results.…”

“…The deviations in the expression of Notch1 and Notch3 may be due to the heterogeneity of the lung cancer samples. Although the study by Huang et al (11), discussed the association between Notch1 and smoking, this correlation remains uncertain due to the relatively insufficient number of smokers with LAC who were recruited to the study. Therefore, a requirement exists to analyze the effect of cigarette smoke on Notch expression in LAC.…”

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

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

“…However, Wael et al (66) found that the Notch 1 receptor can significantly induce apoptosis in SCLC and the A549 adenocarcinoma cell line of NSCLC, while its tumor inhibitory function fails in SCC cells of NSCLC. A recent study demonstrated that the Notch 1 receptor can predict prognosis in lung adenocarcinomas: lower Notch 1 receptor expression in a lung adenocarcinoma cell line and patients with positive Notch 1 receptor expression have a longer survival time and a lower rate of recurrence (67). Taken together, before the role of the Notch 1 receptor in lung cancer can be confirmed, further studies are required.…”