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.
Highlights
According 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 Lung Adenocarcinomas (LADs) is changing from simple morphology into a comprehensive multidisciplinary classification
Despite the recent progresses made in diagnostic techniques and combined treatments for this disease, the overall 5-year survival rate of LAD patients was still less than 30% [3,4,5]
A better understanding the molecular mechanisms involved in the pathogenesis of LAD will be helpful for the development of better prognostic markers and novel therapeutic targets to improve clinical treatment of LAD patients
Summary
According 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). Prognosis of patients can be improved through effective treatment, the 5-year survival rate of patients with advanced lung cancer is only 10%-15% [2]. Non-small cell lung cancer (NSCLC) accounts for 70%-80% in lung cancer, and among them, lung adenocarcinoma (LAD) accounting for almost half of lung cancers, was one of the most common histologic subtype. Despite the recent progresses made in diagnostic techniques and combined treatments for this disease, the overall 5-year survival rate of LAD patients was still less than 30% [3,4,5]. A better understanding the molecular mechanisms involved in the pathogenesis of LAD will be helpful for the development of better prognostic markers and novel therapeutic targets to improve clinical treatment of LAD patients
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