Shin Yup Lee1, Deuk Kju Jung2, Jin Eun Choi3, Cheng Cheng Jin2, Mi Jeong Hong3, Sook Kyung Do2, Hyo-Gyoung Kang3, Won Kee Lee4, Yangki Seok5, Eung Bae Lee5, Ji Yun Jeong6, Kyung Min Shin7, Seung Soo Yoo1, Jaehee Lee8, Seung Ick Cha8, Chang Ho Kim8, Jae Yong Park9. 1. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea. 2. Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu 700-842, Republic of Korea. 3. Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea. 4. Biostatistics Center, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea. 5. Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea; Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea. 6. Department of Pathology, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea. 7. Department of Radiology, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea. 8. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea. 9. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea; Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu 700-842, Republic of Korea. Electronic address: jaeyong@knu.ac.kr.
Abstract
INTRODUCTION: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection. MATERIALS AND METHODS: Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed. RESULTS: Among the 12 SNPs investigated, PD-L1 rs4143815C>G, rs822336G>C, and rs822337T>A were significantly associated with worse survival outcomes in multivariate analyses. When the three SNPs were combined, OS decreased in a dose-dependent manner as the number of bad genotypes increased (Ptrend=0.0003). In the luciferase assay, rs4143815 G allele exhibited a decreased transcription activity compared with C allele (P=0.001), and the rs822336C-rs822337A haplotype had a decreased promoter activity compared with the rs822336G-rs822337T haplotype (P=0.004). Patients with higher expression of PD-L1 mRNA had a better survival compared with lower expression (P=0.03). CONCLUSIONS: PD-L1 polymorphisms may be useful for the prediction of prognosis in patients with surgically resected NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the antitumor immunity and prognosis in NSCLC. Copyright Â
INTRODUCTION: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection. MATERIALS AND METHODS: Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed. RESULTS: Among the 12 SNPs investigated, PD-L1 rs4143815C>G, rs822336G>C, and rs822337T>A were significantly associated with worse survival outcomes in multivariate analyses. When the three SNPs were combined, OS decreased in a dose-dependent manner as the number of bad genotypes increased (Ptrend=0.0003). In the luciferase assay, rs4143815 G allele exhibited a decreased transcription activity compared with C allele (P=0.001), and the rs822336C-rs822337A haplotype had a decreased promoter activity compared with the rs822336G-rs822337T haplotype (P=0.004). Patients with higher expression of PD-L1 mRNA had a better survival compared with lower expression (P=0.03). CONCLUSIONS:PD-L1 polymorphisms may be useful for the prediction of prognosis in patients with surgically resected NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the antitumor immunity and prognosis in NSCLC. Copyright Â