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.

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

“…XRCC1 protein is involved in the BER pathway to repair DNA single-strand breaks combined with three DNA repair enzymes (DNA ligase III, DNA polymerase and PARP) [22,24,35,36]. Recently, evidence has attempted to reveal the underlying biological meaning of common XRCC1 polymorphisms (rs25487, rs25489, rs1799782), but the results of genetic studies are still inconclusive [22,24].…”

DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival

“…It has been reported that genetic Variants and protein expressions might affect the platinum-based chemotherapy response and prognosis of advanced NSCLC patients [36,37]. Platinum-based chemotherapy as a main treatment for lung cancer exerts its anti-cancer effect largely through the formation of bulky platinum-DNA adducts, which result in destabilization of the DNA double helix that otherwise blocks replication and inhibits transcription.…”

The prognostic value of interleukin-17 in lung cancer: A systematic review with meta-analysis based on Chinese patients

“…Furthermore, not all patients can benefit from standard chemotherapy or new targeted therapies. Therefore, finding of efficient biomarkers to choose suitable treatments for individual patient is very significant for patients to acquire the maximum benefit of therapies [ 8 , 9 ].…”