HIF1α genetic variants and protein expressions determine the response to platinum based chemotherapy and clinical outcome in patients with advanced NSCLC

Abstract

Aim: To investigate whether the hypoxia-inducible factor-1α (HIF-1α) genetic variants and protein expression affect the chemotherapy response and the clinical outcome of patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 741 patients with histologically confirmed advanced NSCLC were recruited. Two polymorphisms of HIF-1α gene, namely, the C1772T (P582S) and G1790A (A588T) polymorphisms were determined. The HIF-1α protein expression was determined in 162 different biopsy samples by immunohistochemistry. Results: All patients received platinum-based chemotherapy, 311 were chemotherapy responders and 430 were non-responders. The 1772 CC genotype carriers had a higher chance to be chemotherapy responders compared with those carrying the TT genotype. Patients with high HIF-1α expressions had a significantly higher chance to be non-responder to chemotherapy than those with low HIF-1α expressions. The patients with 1772CC had markedly longer overall survival (OS) and progression free survival (PFS) than those carrying the 1772CT and 1772TT genotype. The HIF-1α expression level was significantly related to the OS, but not PFS. Conclusion: The results of our study suggest that HIF1α genetic variants and protein expression may be used as marker to screen NSCLC patients who are more likely to be responder to platinum based chemotherapy. © 2013 S. Karger AG, Basel.