title: The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs.
abstract: BACKGROUND
  Recent clinical trials have shown that immune-checkpoint blockade yields remarkable response in a subset of non-small cell lung cancer (NSCLC) patients. However, few studies directly focus on the association between epidermal growth factor receptor (EGFR) mutational status and programmed cell death-ligand 1 (PD-L1) expression. We examined whether PD-L1 is related to clinicopathologic factors and prognosis in patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs).
  
  
  METHODS
  One-hundred and seventy patients with advanced NSCLC were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. EGFR mutation was examined by fluorescent quantitative polymerase chain reaction (PCR). The correlations between PD-L1 expression and EGFR status and survival parameters were analyzed.
  
  
  RESULTS
  The overall frequency of PD-L1 over-expression was 65.9% (112/170). In lung adenocarcinoma, PD-L1 tended to be associated with mutant EGFR (PD-L1 overexpression in mutant and wild-type EGFR, 64/89 (71.9%) vs. 32/56 (57.1%), respectively; p=0.067). Subgroup analyses showed that high PD-L1 expression was associated with significantly shorter overall survival (OS) in EGFR wild-type patients (p=0.029) but not in EGFR mutant patients (p=0.932) treated with EGFR-TKIs. Even more, for EGFR mutant patients, higher expression of PD-L1 might only signal better outcome with TKIs.
  
  
  CONCLUSIONS
  High PD-L1 expression was likely to be associated with the presence of EGFR mutation in advanced lung adenocarcinoma. For EGFR wild-type patients, the PD-L1 over expression can be considered as a poor prognostic indicator of OS.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Key Laboratory for Stem Cells and Tissue Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, China.
authors.forename: Peijian
authors.initials: P
authors.lastname: Peng
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR status; NSCLC; PD-L1; TKI; prognosis