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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

  • Authors:
    • Anna Grenda
    • Paweł Krawczyk
    • Tomasz Kucharczyk
    • Justyna Błach
    • Katarzyna Reszka
    • Izabela Chmielewska
    • Jarosław Buczkowski
    • Robert Kieszko
    • Jan Siwiec
    • Tomasz Kubiatowski
    • Aleksandra Bożyk
    • Kinga Krukowska
    • Bożena Jarosz
    • Iwona Paśnik
    • Juliusz Pankowski
    • Daria Świniuch
    • Katarzyna Stencel
    • Michał Gil
    • Kinga Lew
    • Rodryg Ramlau
    • Aleksandra Szczęsna
    • Sebastian Fidler
    • Andrzej Sieracki
    • Andrzej Każarnowicz
    • Piotr Serwatowski
    • Tomasz Grodzki
    • Janusz Milanowski
  • View Affiliations / Copyright

    Affiliations: Chair and Department of Pneumology, Oncology and Allergology, Medical University of Lublin, 20‑090 Lublin, Poland, Institute of Genetics and Immunology Genim LCC, 20‑609 Lublin, Poland, Department of Clinical Oncology, Saint Jan of Dukla Oncology Centre of the Lublin Region, 20‑090 Lublin, Poland, Chair and Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, 20‑090 Lublin, Poland, Chair and Department of Clinical Pathomorphology, Medical University of Lublin, 20‑090 Lublin, Poland, Department of Pathology, Specialist Hospital for Lung Diseases ‘Rebirth’ Klara Jelska, 34‑500 Zakopane, Poland, Chair and Department of Clinical Oncology, Poznań University of Medical Sciences, 60‑569 Poznań, Poland, Department of Lung Diseases with Oncology Subdivision, Mazovian Center for the Treatment of Lung Diseases and Tuberculosis, 60‑569 Otwock, Poland, Department of Oncology, Provincial Hospital Center of The Jeleniogórska Valley, 58‑506 Jelenia Góra, Poland, Department of Clinical Oncology, Independent Public Provincial Hospital Pope John Paul II in Zamość, 22‑404 Zamość, Poland, Department of Oncology, Chemotherapy Subdivision, Independent Public Group of Tuberculosis and Pulmonary Diseases in Olsztyn, 10‑357 Olsztyn, Poland, Department of Clinical Oncology and Chemotherapy, Pomeranian Medical University, 70‑891 Szczecin, Poland, Chair and Department of Thoracic Surgery, Pomeranian Medical University, 70‑891 Szczecin, Poland
    Copyright: © Grenda et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 449
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    Published online on: April 7, 2021
       https://doi.org/10.3892/ol.2021.12710
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Abstract

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 PD‑L1 and two single nucleotide polymorphisms (SNPs), rs822335 and rs822336, in the promoter of PD‑L1 by quantitative PCR in 673 patients with NSCLC. Overall survival time of patients with NSCLC depending on the assessed predictive factors (PD‑L1 CNV or SNP) and the treatment methods (immunotherapy in first/second line of treatment or chemotherapy) was analyzed. The present study revealed significantly higher PD‑L1 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 PD‑L1 copies number, genotype of rs822335 PD‑L1 polymorphism and PD‑L1 protein expression on tumor cells. However, the impact of CNV and SNPs of PD‑L1 on overall survival of patients with NSCLC requires further investigation.
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Copy and paste a formatted citation
Spandidos Publications style
Grenda A, Krawczyk P, Kucharczyk T, Błach J, Reszka K, Chmielewska I, Buczkowski J, Kieszko R, Siwiec J, Kubiatowski T, Kubiatowski T, et al: 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. Oncol Lett 21: 449, 2021.
APA
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I. ... Milanowski, J. (2021). 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. Oncology Letters, 21, 449. https://doi.org/10.3892/ol.2021.12710
MLA
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I., Buczkowski, J., Kieszko, R., Siwiec, J., Kubiatowski, T., Bożyk, A., Krukowska, K., Jarosz, B., Paśnik, I., Pankowski, J., Świniuch, D., Stencel, K., Gil, M., Lew, K., Ramlau, R., Szczęsna, A., Fidler, S., Sieracki, A., Każarnowicz, A., Serwatowski, P., Grodzki, T., Milanowski, J."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". Oncology Letters 21.6 (2021): 449.
Chicago
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I., Buczkowski, J., Kieszko, R., Siwiec, J., Kubiatowski, T., Bożyk, A., Krukowska, K., Jarosz, B., Paśnik, I., Pankowski, J., Świniuch, D., Stencel, K., Gil, M., Lew, K., Ramlau, R., Szczęsna, A., Fidler, S., Sieracki, A., Każarnowicz, A., Serwatowski, P., Grodzki, T., Milanowski, J."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". Oncology Letters 21, no. 6 (2021): 449. https://doi.org/10.3892/ol.2021.12710
Copy and paste a formatted citation
x
Spandidos Publications style
Grenda A, Krawczyk P, Kucharczyk T, Błach J, Reszka K, Chmielewska I, Buczkowski J, Kieszko R, Siwiec J, Kubiatowski T, Kubiatowski T, et al: 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. Oncol Lett 21: 449, 2021.
APA
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I. ... Milanowski, J. (2021). 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. Oncology Letters, 21, 449. https://doi.org/10.3892/ol.2021.12710
MLA
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I., Buczkowski, J., Kieszko, R., Siwiec, J., Kubiatowski, T., Bożyk, A., Krukowska, K., Jarosz, B., Paśnik, I., Pankowski, J., Świniuch, D., Stencel, K., Gil, M., Lew, K., Ramlau, R., Szczęsna, A., Fidler, S., Sieracki, A., Każarnowicz, A., Serwatowski, P., Grodzki, T., Milanowski, J."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". Oncology Letters 21.6 (2021): 449.
Chicago
Grenda, A., Krawczyk, P., Kucharczyk, T., Błach, J., Reszka, K., Chmielewska, I., Buczkowski, J., Kieszko, R., Siwiec, J., Kubiatowski, T., Bożyk, A., Krukowska, K., Jarosz, B., Paśnik, I., Pankowski, J., Świniuch, D., Stencel, K., Gil, M., Lew, K., Ramlau, R., Szczęsna, A., Fidler, S., Sieracki, A., Każarnowicz, A., Serwatowski, P., Grodzki, T., Milanowski, J."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". Oncology Letters 21, no. 6 (2021): 449. https://doi.org/10.3892/ol.2021.12710
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