Impact of copy number variant and single nucleotide polymorphism of the programmed death-ligand 1 gene, programmed death-ligand 1 protein expression and therapy regimens on overall survival in a large group of Caucasian patients with non-small cell lung carcinoma

Anti-programmed death-1 or anti-programmed death-ligand 1 (PD-L1) blockade may be ineffective in some patients with non-small cell lung cancer (NSCLC) with high percentage of tumor cells with PD-L1 expression. In addition, immunotherapy may provide great benefits in patients without PD-L1 expression...

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Published in:	Oncology letters Vol. 21; no. 6; p. 449
Main Authors:	Grenda, Anna, Krawczyk, Paweł, Kucharczyk, Tomasz, Błach, Justyna, Reszka, Katarzyna, Chmielewska, Izabela, Buczkowski, Jarosław, Kieszko, Robert, Siwiec, Jan, Kubiatowski, Tomasz, Bożyk, Aleksandra, Krukowska, Kinga, Jarosz, Bożena, Paśnik, Iwona, Pankowski, Juliusz, Świniuch, Daria, Stencel, Katarzyna, Gil, Michał, Lew, Kinga, Ramlau, Rodryg, Szczęsna, Aleksandra, Fidler, Sebastian, Sieracki, Andrzej, Każarnowicz, Andrzej, Serwatowski, Piotr, Grodzki, Tomasz, Milanowski, Janusz
Format:	Journal Article
Language:	English
Published:	Greece Spandidos Publications 01-06-2021 Spandidos Publications UK Ltd D.A. Spandidos
Subjects:	Binding sites Cancer Cancer therapies Care and treatment Chemotherapy Chromosomes Clinical trials Cloning Gene expression Genetic aspects Hospitals Immunohistochemistry Immunotherapy Kinases Ligands Lung cancer Lung cancer, Non-small cell Lung diseases Medical equipment and supplies industry Medical research Medical test kit industry Medicine, Experimental Metastasis Monoclonal antibodies Oncology Patient outcomes Protein expression Proteins Scientific equipment and supplies industry Single nucleotide polymorphisms Tuberculosis Ultrasonic imaging Poland United States Europe non-small cell lung cancer programmed death-ligand 1 copy number variation single nucleotide polymorphism protein expression
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Summary:	Anti-programmed death-1 or anti-programmed death-ligand 1 (PD-L1) blockade may be ineffective in some patients with non-small cell lung cancer (NSCLC) with high percentage of tumor cells with PD-L1 expression. In addition, immunotherapy may provide great benefits in patients without PD-L1 expression. The present study assessed PD-L1 protein expression by immunohistochemistry, copy number variation (CNV) of and two single nucleotide polymorphisms (SNPs), rs822335 and rs822336, in the promoter of by quantitative PCR in 673 patients with NSCLC. Overall survival time of patients with NSCLC depending on the assessed predictive factors ( CNV or SNP) and the treatment methods (immunotherapy in first/second line of treatment or chemotherapy) was analyzed. The present study revealed significantly higher copies number in patients with ≥10% and ≥50% of tumor cells with PD-L1 expression compared to patients with lower percentage of PD-L1-positive tumor cells (P=0.02 and P=0.0002, respectively). There was a significant positive correlation (R=0.2; P=0.01) between number of PD-L1 copies and percentage of tumor cells with PD-L1 protein expression. Percentage of tumor cells with PD-L1 expression was lower in patients with TT genotype of the rs822335 polymorphism compared to those with CC genotype (P=0.03). The present study observed significantly higher risk of death in patients treated with chemotherapy compared to those treated with immunotherapy (P<0.0001; hazard ratio=2.4768; 95% confidence interval, 2.0120-3.0490). The present study demonstrated a close relationship between copies number, genotype of rs822335 polymorphism and PD-L1 protein expression on tumor cells. However, the impact of CNV and SNPs of on overall survival of patients with NSCLC requires further investigation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1792-1074 1792-1082
DOI:	10.3892/ol.2021.12710