The genomic mutational landscape and its correlation with TMB, PD-L1 expression and CD8+ T cell infiltration in Chinese lung large cell neuroendocrine carcinoma.
Lung Cancer
; 166: 161-169, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35287068
ABSTRACT
OBJECTIVES:
The aim of this study was to illustrate the genomic mutational landscape, tumor mutation burden (TMB), PD-L1 expression, CD8+ T cell infiltration and their prognostic value in resectable Lung large cell neuroendocrine carcinoma (LCNEC). MATERIALS ANDMETHODS:
The tumor tissues and corresponding normal tissues of 37 LCNEC patients undergoing surgical resection were collected and determined by whole exome sequencing (WES). Subsequently, the tumor samples were stained with the antibodies of PD-L1 and CD8 via multiplex immunohistochemistry (Multi IHC) to evaluate PD-L1 expression and CD8+ T cells infiltration in stroma and tumor regions. Univariate and multivariate analysis were applied to assess the association among genomic features, immune profiles, clinical data and prognosis of LCNEC patients.RESULTS:
The median TMB was 5.42 mutations per megabase. Mutations in Wnt (p = 0.049) and Hippo (p = 0.005) pathways were markedly associated with higher TMB value, mutations in p53 pathway were related with higher stromal PD-L1 expression (p = 0.041). LCNEC patients with KEAP1 mutation (p = 0.044) or without adjuvant radiochemotherapy (p = 0.023) had significantly shorter OS. Multivariate analysis showed that high stromal CD8 + T cells infiltration was an independent favorable factor for disease free survival (p = 0.030). The patient stratification of KEAP1 mutation status and stroma PD-L1 expression was independent prognostic factors for overall survival (p = 0.049).CONCLUSION:
The investigation of prognostic factor in resectable LCNEC may provide guidance for timely intervention and new therapy strategy for LCENC patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Neuroendócrino
/
Carcinoma de Células Grandes
/
Antígeno B7-H1
/
Neoplasias Pulmonares
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China