title: PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.
abstract: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatin chemotherapy. A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Among the 12 SNPs investigated, PD-L1 rs2297136T > C and rs4143815C > G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T > C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C > G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. PD-L1 rs2297136T > C and rs4143815C > G polymorphisms may be useful for the prediction of clinical outcome of 1(st) line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients.
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea.|Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 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, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.|Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 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, School of Medicine, Kyungpook National University, 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: Mi Jeong
authors.initials: MJ
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 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, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.|Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Biostatistics Center, School of Medicine, Kyungpook National University, 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, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Shin
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea.|Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu 702-201, Republic of Korea.|Departments of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.|Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, 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.|Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-842, Republic of Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D017239:Paclitaxel / Q000627:therapeutic use; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017239:Paclitaxel; D002945:Cisplatin