Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Abstract

Kai-Yi Tao,1 Xian-Xing Li,2 Wei-Zhen Xu,3 Yin Wang,4 Shuang-Mei Zhu,5 Hua-Xia Xie,3 Wen-Hua Luo,6 Yan-Jun Xu,7 Xiao-Ling Xu3,7 1Department of Thoracic Surgery, 2Department of Radiology, 3Key Laboratory on Diagnosis and Treatment Technology on Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute), 4Physical Examination Center, Zhejiang Provincial People’s Hospital, Hangzhou, 5Department of Radio-Chemotherapy Oncology, Lishui People’s Hospital, Sixth Affiliated Hospital of Wenzhou Medical University, 6Department of Radio-Chemotherapy Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 7Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Background: Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms – FAS −670 A>G, FAS ligand −844 T>C, survivin −31 G>C, and survivin 9386 C>T – with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy. Materials and methods: Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique.Results: Patients with the CC genotype of FAS −670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS −670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively).Conclusion: The functional FAS −670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. Keywords: lung cancer, FAS −670 A>G, survivin 9386 C>T, polymorphism, chemotherapy response