Notch 3 Protein, not its Gene Polymorphism, is Associated with the Chemotherapy Response and Prognosis of Advanced NSCLC Patients

Aim: To study the relation of NOTCH3 and its gene polymorphisms with the chemotherapy response and the prognosis of patients with Non small cell lung cancer (NSCLC). Methods: A total of 594 patients with advanced stage of NSCLC (IIIA, IIIB and IV) NSCLC were enrolled. All patients received Platinum-based chemotherapy. The NOTCH3 expression in tumors and its gene polymorphisms were determined. In vitro, several NSCLC cell lines received the NOTCH3 over expression vector and small interfering RNA (siRNA) to study the role of NOTCH3 in regulation the cellular biological behaviors. Results: The genotype and the allele frequencies of NOTCH3 gene polymorphisms at 605C>T and 1735T>C were not significantly different between good responders and poor responders to chemotherapy. However, high NOTCH3 expression in tumor represented a significantly higher possibility of being resistant to chemotherapy. Also, patients with high NOTCH3 expression had a poorer prognosis than those with low NOTCH3 expression. In vitro studies showed that NOTCH3 inhibition dramatically suppressed the proliferation, migration, invasiveness abilities and prompted apoptosis in NSCLC cells. Conclusion: NOTCH3 regulates the cellular behavior, including, proliferation, migration, invasiveness abilities and apoptosis of NSCLC cells. NOTCH3 may be used as a marker to predict the chemotherapy response and prognosis of advanced NSCLC. Copyright (C) 2014 S. Karger AG, Basel