Polymorphism of Baculoviral Inhibitor of Apoptosis Repeat-Containing 5 (BIRC5) Can Be Associated with Clinical Outcome of Non-Small Cell Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) comprises about 85% of all lung cancers. Currently, NSCLC therapy is based on the analysis of specific predictors, whose presence qualifies patients for appropriate treatment. Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), also known as “survivin”, is a protein whose expression is characteristic for most malignant tumors and fetal tissue, while absent in mature cells. The biological role of BIRC5 is to counteract apoptosis by inhibiting the initiating and effector activities of caspases and binding to microtubules of the mitotic spindle. In our study, we looked for a relationship between BIRC5 gene polymorphism and the effectiveness of platinum-based chemotherapy. The study group consisted of 104 patients with newly diagnosed locally advanced or metastatic NSCLC. DNA was isolated from pretreatment blood samples, and SNPs of BIRC5 gene were analyzed. All patients received first-line platinum-based chemotherapy. Univariate analysis showed that a specific BIRC5 genotype was significantly associated with a higher risk of early progression (homozygous GG vs. heterozygous CG or CC: 28.9% vs. 11.9%). The presence of a homozygous GG genotype of the BIRC5 gene was insignificantly related to PFS shortening and TTP shortening. Moreover, significantly higher risk of overall survival shortening was associated with the BIRC5 homozygous GG genotype. Thus, studies on polymorphisms of selected genes affecting apoptosis may have a practical benefit for clinicians who monitor and treat NSCLC.

Keywords

• BIRC5
• Survivin
• NSCLC
• outcome