Relevance of pd-l1 non-coding polymorphisms on the prognosis of a genetically admixed nsclc cohort

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorThe University of Texas MD Anderson Cancer Center-
Autor(es): dc.contributorAC Camargo Cancer Center-
Autor(es): dc.contributorCancer Institute of São Paulo (ICESP)-
Autor(es): dc.creatorMachado-Rugolo, Juliana [UNESP]-
Autor(es): dc.creatorPrieto, Tabatha Gutierrez-
Autor(es): dc.creatorFabro, Alexandre Todorovic-
Autor(es): dc.creatorCuentas, Edwin Roger Parra-
Autor(es): dc.creatorSá, Vanessa Karen-
Autor(es): dc.creatorBaldavira, Camila Machado-
Autor(es): dc.creatorRainho, Claudia Aparecida [UNESP]-
Autor(es): dc.creatorCastelli, Erick C. [UNESP]-
Autor(es): dc.creatorFarhat, Cecilia-
Autor(es): dc.creatorTakagaki, Teresa Yae-
Autor(es): dc.creatorNagai, Maria Aparecida-
Autor(es): dc.creatorCapelozzi, Vera Luiza-
Data de aceite: dc.date.accessioned2022-02-22T00:49:53Z-
Data de disponibilização: dc.date.available2022-02-22T00:49:53Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2020-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.2147/PGPM.S286717-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/207324-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/207324-
Descrição: dc.descriptionPurpose: Although non-small cell lung cancer (NSCLC) remains a deadly disease, new predictive biomarkers have emerged to assist in managing the disease, of which one of the most promising is the programmed death-ligand 1 (PD-L1). Each, PD-L1 variant seem to modulate the function of immune checkpoints differently and affect response to adjuvant treatment and outcome in NSCLC patients. We thus investigated the influence of these PD-L1 genetic variations in genetically admixed NSCLC tissue samples, and correlated these values with clinicopathological characteristics, including prognosis. Materials and Methods: We evaluated PD-L1 non-coding genetic variants and protein expression in lung adenocarcinomas (ADC), squamous cell carcinomas (SqCC), and large cell carcinomas (LCC) in silico. Microarray paraffin blocks from 70 samples of ADC (N=33), SqCC (N=24), and LCC (N=13) were used to create PD-L1 multiplex immunofluorescence assays with a Cell Signaling E1L3N clone. Fifteen polymorphisms of the PD-L1 gene were investigated by targeted sequencing and evaluated in silico using dedicated tools. Results: Although PD-L1 polymorphisms seemed not to interfere with protein expression, PD-L1 expression varied among different histological subtypes, as did clinical outcomes, with the rs4742098A>G, rs4143815G>C, and rs7041009G>A variants being associated with relapse (P=0.01; P=0.05; P=0.02, respectively). The rs7041009 GG genotype showed a significant correlation with younger and alive patients compared to carriers of the A allele (P=0.02 and P<0.01, respectively). The Cox regression model showed that the rs7041009 GG genotype may influence OS (P<0.01) as a co-dependent factor associated with radiotherapy and recurrence in NSCLC patients. Furthermore, the Kaplan–Meier survival curves showed that rs7041009 and rs4742098 might impact PPS in relapsed patients. In silico approaches identified the variants as benign. Conclusion: PD-L1 non-coding variants play an important role in modulating immune checkpoint function and may be explored as immunotherapy biomarkers. We highlight the rs7041009 variant, which impacts OS and PPS in NSCLC patients.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionLaboratory of Genomics and Histomorphometry Department of Pathology University of São Paulo Medical School (USP)-
Descrição: dc.descriptionHealth Technology Assessment Center Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Pathology and Legal Medicine Ribeirão Preto School of Medicine University of São Paulo (FMRP-USP)-
Descrição: dc.descriptionDepartment of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center-
Descrição: dc.descriptionLaboratory of Genomics and Molecular Biology Centro Internacional De Pesquisa (CIPE) AC Camargo Cancer Center-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionMolecular Genetics and Bioinformatics Laboratory Experimental Research Unit (UNIPEX) Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Pathology Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionDivision of Pneumology Heart Institute (Incor) Clinical Hospital University of São Paulo Medical School (USP)-
Descrição: dc.descriptionDepartment of Radiology and Oncology University of São Paulo Medical School (USP)-
Descrição: dc.descriptionLaboratory of Molecular Genetics Center for Translational Research in Oncology Cancer Institute of São Paulo (ICESP)-
Descrição: dc.descriptionHealth Technology Assessment Center Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionMolecular Genetics and Bioinformatics Laboratory Experimental Research Unit (UNIPEX) Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Pathology Medical School of São Paulo State University (UNESP)-
Descrição: dc.descriptionFAPESP: 2013/14277-4-
Descrição: dc.descriptionFAPESP: 2018/20403-6-
Formato: dc.format239-252-
Idioma: dc.languageen-
Relação: dc.relationPharmacogenomics and Personalized Medicine-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectNext-generation sequencing-
Palavras-chave: dc.subjectNon-small cell lung cancer-
Palavras-chave: dc.subjectPD-L1-
Palavras-chave: dc.subjectSingle nucleotide polymorphisms-
Título: dc.titleRelevance of pd-l1 non-coding polymorphisms on the prognosis of a genetically admixed nsclc cohort-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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