Abstract 4213: Molecular biomarker study of programmed death receptor ligand 1 (PD-L1) in Korean patients with lung adenocarcinoma
Authors: Liu Xiaoqiao , Lee Jinseon , Lee Soo Jung , Cho Jong Ho , Sun Jong-Mu , Zhang Lu , Pei Yunfei , Chen Lan , Dolled-Filhart Marisa , Emancipator Kenneth , Lunceford Jared , Chen Ronghua , Zhou Wei , Kim Jhingook 
Published: August 2018

Abstract
Purpose We explored the association between different molecular biomarkers and PD-L1 mRNA and protein expression in Asian patients with lung adenocarcinoma.
Experimental design PD-L1 protein expression level was evaluated using a prototype immunohistochemistry (IHC) assay with the 22C3 antibody in tumor samples from 157 patients with lung adenocarcinoma from Samsung Medical Center. Other biomarkers, including PD-L1, PD-L2 and IFN-γ mRNA expression detected using the Affymetrix array, EGFR and KRAS mutation detected using the Sequenom platform, ALK fusion detected using the NanoString system and tumor mutation burden (TMB) calculated as total number of non-synonymous single nucleotide substitution from Illumina HiSeq 2000 sequencing platform were provided as part of the Asian Cancer Research Group collaboration. Spearman correlation test, t test, Fisher exact test, and multivariate regression models were utilized to test the association between different biomarkers and PD-L1 mRNA/protein expression. PD-L1 IHC tumor proportion score was analyzed as a continuous or categorical variable, where PD-L1 strong and weak positivity were defined to be traceable to the 1% and 50% cutoffs used in the clinical trial version of the assay.
Results The median age was 61 years (range, 20-84), 50% were female, 40% were smokers, and 77% had stage I/II disease. There was strong correlation between PD-L1 mRNA and protein expression (N = 79, Spearman R = 0.762, P &lt; 0.0001). Absence of EGFR mutation was associated with higher PD-L1 expression (for mRNA, N = 166, t test P = 0.023; for protein, N = 83, Fisher test P = 0.051), and presence of ALK fusion was associated with higher PD-L1 expression (for mRNA, N = 229, t test P = 0.001; for protein, N = 144, Fisher test P = 0.002). Similar associations between EGFR mutation, ALK fusion, and PD-L1 mRNA and protein expression were observed after adjusting for age, sex, smoking status, and disease stage. No association was found between PD-L1 expression and KRAS mutation (for mRNA, N = 140, t test P = 0.305; for protein, N = 78, Fisher test P = 0.243). mRNA expression of PD-L2, the other PD-1 ligand, was highly correlated with PD-L1 expression (for mRNA, N = 253, Spearman R = 0.650, P &lt; 0.0001; for protein, N = 79, Spearman R = 0.444, P &lt; 0.0001). As evidence for IFN-γ-inducible biology, IFN-γ mRNA expression was significantly correlated with PD-L1 expression (for mRNA, N = 253, Spearman R = 0.57, P &lt; 0.0001; for protein, N = 79, Spearman R = 0.44, P &lt; 0.0001). TMB was not significantly correlated with PD-L1 expression (for mRNA, N = 31, Spearman R = 0.092, P = 0.62; for protein, N = 8, Spearman R = 0.19, P = 0.65), which suggested independent predictive ability for anti-PD-1 therapy.
Conclusion Our study provides evidence that DNA and RNA features, including PD-L1 mRNA, lack of EGFR mutation, and ALK fusion are associated with PD-L1 protein expression for Asian lung adenocarcinoma patients.
Citation Format: Xiaoqiao Liu, Jinseon Lee, Soo Jung Lee, Jong Ho Cho, Jong-Mu Sun, Lu Zhang, Yunfei Pei, Lan Chen, Marisa Dolled-Filhart, Kenneth Emancipator, Jared Lunceford, Ronghua Chen, Wei Zhou, Jhingook Kim. Molecular biomarker study of programmed death receptor ligand 1 (PD-L1) in Korean patients with lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4213.