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, marker to predict the chemotherapy response and prognosis of advanced NSCLC. marker to predict the chemotherapy response and prognosis of advanced NSCLC.

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