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Br J Cancer ; 119(8): 950-960, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30318514

RESUMO

BACKGROUND: No study has evaluated the predictive and prognostic role of CD8 and PD-L1 coexpression in non-small-cell lung cancer (NSCLC). METHODS: We analyzed RNA sequencing and/or immunohistochemistry staining in NSCLC patients from The Cancer Genome Atlas (n = 1016), and 34 metastatic NSCLC samples not treated by immunotherapy as prognostic cohorts. As predictive aspect of CD8 and PD-L1, we used 85 NSCLC patients treated with anti-PD-1. Two validation cohorts were used including 44 NSCLC patients treated with anti-PD-1 and an external cohort with different tumor types. RESULTS: In prognostic cohorts, high CD8A expression was associated with longer OS (p = 0.02), while high CD274 mRNA was associated with poor prognosis (p = 0.05). In predictive cohort, high CD8 expression and CD8A mRNA were associated with longer progression-free survival (PFS) (p = 0.0002). There was no significant association between PD-L1 expression and PFS while high CD274 mRNA was associated with longer PFS (p = 0.009). A combination of CD8A and CD274 was highly predictive of outcome. These results were confirmed in the validation cohorts. This two-genes signature demonstrated similar results compared to gold standard signatures. CONCLUSION: CD8 represents both a prognostic and predictive factor of outcomes, while PD-L1 share different prognostic and predictive roles.


Assuntos
Antígeno B7-H1/análise , Antígenos CD8/análise , Linfócitos T CD8-Positivos/citologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Antígenos CD8/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , RNA Mensageiro/genética , Estudos Retrospectivos
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