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PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphism...

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Autores principales: Makrantonakis, Andreas-Evangelos, Zografos, Eleni, Gazouli, Maria, Dimitrakakis, Konstantinos, Toutouzas, Konstantinos G., Zografos, Constantinos G., Kalapanida, Despoina, Tsiakou, Andriani, Samelis, George, Zagouri, Flora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612177/
https://www.ncbi.nlm.nih.gov/pubmed/36295559
http://dx.doi.org/10.3390/medicina58101399
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author Makrantonakis, Andreas-Evangelos
Zografos, Eleni
Gazouli, Maria
Dimitrakakis, Konstantinos
Toutouzas, Konstantinos G.
Zografos, Constantinos G.
Kalapanida, Despoina
Tsiakou, Andriani
Samelis, George
Zagouri, Flora
author_facet Makrantonakis, Andreas-Evangelos
Zografos, Eleni
Gazouli, Maria
Dimitrakakis, Konstantinos
Toutouzas, Konstantinos G.
Zografos, Constantinos G.
Kalapanida, Despoina
Tsiakou, Andriani
Samelis, George
Zagouri, Flora
author_sort Makrantonakis, Andreas-Evangelos
collection PubMed
description Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.
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spelling pubmed-96121772022-10-28 PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients Makrantonakis, Andreas-Evangelos Zografos, Eleni Gazouli, Maria Dimitrakakis, Konstantinos Toutouzas, Konstantinos G. Zografos, Constantinos G. Kalapanida, Despoina Tsiakou, Andriani Samelis, George Zagouri, Flora Medicina (Kaunas) Article Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival. MDPI 2022-10-06 /pmc/articles/PMC9612177/ /pubmed/36295559 http://dx.doi.org/10.3390/medicina58101399 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Makrantonakis, Andreas-Evangelos
Zografos, Eleni
Gazouli, Maria
Dimitrakakis, Konstantinos
Toutouzas, Konstantinos G.
Zografos, Constantinos G.
Kalapanida, Despoina
Tsiakou, Andriani
Samelis, George
Zagouri, Flora
PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title_full PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title_fullStr PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title_full_unstemmed PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title_short PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients
title_sort pd-l1 gene polymorphisms rs822336 g>c and rs822337 t>a: promising prognostic markers in triple negative breast cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612177/
https://www.ncbi.nlm.nih.gov/pubmed/36295559
http://dx.doi.org/10.3390/medicina58101399
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