PD-L1 gene copy number and promoter polymorphisms regulate PD-L1 expression in tumor cells of non-small cell lung cancer patients

• Published in: Cancer genetics 2019-09, Vol.237, p.10-18
• Main Authors: Krawczyk, Paweł, Grenda, Anna, Wojas-Krawczyk, Kamila, Nicoś, Marcin, Kucharczyk, Tomasz, Jarosz, Bożena, Reszka, Katarzyna, Pankowski, Juliusz, Krukowska, Kinga, Bożyk, Aleksandra, Szumiło, Justyna, Sawicki, Marek, Trojanowski, Tomasz, Milanowski, Janusz
• Format: Article
• Language: English
• Subjects: Aged; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Carcinoma, Non-Small-Cell Lung - genetics; DNA Copy Number Variations; Female; Gene copy number; Humans; Lung Neoplasms - genetics; Male; Middle Aged; PD-L1 in NSCLC; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; RNA, Messenger - genetics; Single nucleotide polymorphisms
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2019.06.001

•The polymorphisms of PD-L1 gene and PD-L1 gene copy number could be responsible for PD-L1 mRNA and protein expression.•Patients with CC genotype in rs822335 had significantly (p = 0.043) higher percentage of tumor cells with PD-L1 expression (test with 22C3 antibody) than patients with CT or TT genotypes.•PD-L1 gene polymorphisms and PD-L1 gene copy number may be a predictor for PD-L1 protein expression on tumor cells. Most drugs targeting PD-1 or PD-L1 are more effective when cancer cells of non-small cell lung cancer (NSCLC) patients express PD-L1 protein. The polymorphisms of PD-L1 gene and PD-L1 gene copy number could be responsible for PD-L1 mRNA and protein expression. We analyzed PD-L1 protein expression using two IHC assays, mRNA (PD-L1) expression by qRT-PCR, PD-L1 gene promoter region polymorphisms (rs822335 and rs822336) by qPCR and PD-L1 gene copy number by fluorescence in situ hybridization method. Patients with CC genotype in rs822335 had significantly (p = 0.043) higher percentage of tumor cells with PD-L1 expression (test with 22C3 antibody) than patients with CT or TT genotypes. PD-L1 gene copy number significantly positively correlated with percentage of tumor cells with PD-L1 expression detected in tests with 22C3 antibody (p = 0.005, R = +0.442) and with SP142 antibody (p = 0.021, R = +0.369). PD-L1 gene copy number did not correlate with PD-L1 mRNA expression. Patients with PD-L1 expression tested with 22C3 antibody had significantly higher expression of PD-L1 mRNA (p = 0.023), number of chromsosme 9 centromeres (p = 0.023) and PD-L1 gene copy number (p = 0.003) than patients without PD-L1 expression on tumor cells PD-L1 gene polymorphisms and PD-L1 gene copy number may be a predictor for PD-L1 protein expression on tumor cells.