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

Publication date: Available online 8 June 2019Source: Cancer GeneticsAuthor(s): Paweł Krawczyk, Anna Grenda, Kamila Wojas-Krawczyk, Marcin Nicoś, Tomasz Kucharczyk, Bożena Jarosz, Katarzyna Reszka, Juliusz Pankowski, Kinga Krukowska, Aleksandra Bożyk, Justyna Szumiło, Marek Sawicki, Tomasz Trojanowski, Janusz MilanowskiAbstractMost 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 hybridisation 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=0.00...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research