title: Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Deuk Kju
authors.initials: DK
authors.lastname: Jung
authors.affiliation: 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.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Cheng Cheng
authors.initials: CC
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Hong
authors.affiliation: 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.
authors.forename: Sook Kyung
authors.initials: SK
authors.lastname: Do
authors.affiliation: 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.
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Biostatistics Center, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Yangki
authors.initials: Y
authors.lastname: Seok
authors.affiliation: 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.
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Radiology, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Shin
authors.affiliation: 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.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea.
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-842, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Lung cancer; PD-L1; Polymorphism; Prognosis