Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden.
Adult
Aged
Aged, 80 and over
B7-H1 Antigen
/ metabolism
Biomarkers, Tumor
/ metabolism
Carcinoma, Non-Small-Cell Lung
/ genetics
DNA Helicases
/ metabolism
DNA Mutational Analysis
DNA-Binding Proteins
/ metabolism
Female
Humans
Lung Neoplasms
/ genetics
Male
Middle Aged
Mutation
Nuclear Proteins
/ metabolism
Prognosis
Retrospective Studies
Survival Rate
Transcription Factors
/ metabolism
Clinicopathological feature
PD-L1 expression
SWI/SNF complex
Tissue microarray
Tumor mutation burden
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
14
07
2019
revised:
06
10
2019
accepted:
08
10
2019
pubmed:
21
10
2019
medline:
2
9
2020
entrez:
21
10
2019
Statut:
ppublish
Résumé
Loss of the chromatin remodeling SWItch/Sucrose Non-fermentable (SWI/SNF) complex is implicated in the pathogenesis of several types of neoplasms. The aim of this study was to examine the clinicopathological features of non-small cell lung cancer (NSCLC) with loss of expression of the SWI/SNF complex. Specimens from a total 1013 NSCLC cases used for tissue microarrays (TMAs) were immunohistochemically examined for expression of SWI/SNF complex (BAF) subunits, namely SMARCA4, SMARCA2, ARID1A, and ARID1B. We examined the clinicopathological features and PD-L1 expression status in NSCLC cases with loss of expression of one or more subunits of the SWI/SNF complex (BAF-Loss). Moreover, we compared the tumor mutation burden (TMB) between NSCLC cases with BAF-Loss and those with intact expression of the four subunits (BAF-Intact). Using TMA, BAF-Loss was observed in 5.4% of cases (SMARCA4: 2.4%, SMARCA2: 2.4%, ARID1A: 1.3%, and ARID1B: 0.3%). Concurrent loss of expression of two or more subunits of the SWI/SNF complex was detected in 0.7% of cases. BAF-Loss was significantly associated with smoking history, young age, male sex, pulmonary emphysema/bullae, large invasive tumor size, pleural invasion, vascular invasion, solid-predominant morphology, and absence of a lepidic growth component. A higher proportion of PD-L1-positive cases was observed among NSCLC patients with BAF-Loss than BAF-Intact (42% vs 26%, P < 0.01). In stage I NSCLC, SWI/SNF-Loss (n = 23) was associated with shorter overall survival (HR: 2.43; 95% CI: 1.18-5.01; P = 0.01) and recurrence-free survival (HR: 2.22; 95% CI: 1.17-4.24; P < 0.01) compared to BAF-Intact (n = 563). The degree of TMB was significantly higher among NSCLC patients with BAF-Loss (n = 3) than BAF-Intact (n = 7) (median 437 vs 113 mutations/whole-exome, P = 0.02). The current results suggest that loss of SWI/SNF expression in NSCLC is associated with aggressive clinicopathological features, PD-L1-positive status and high TMB.
Identifiants
pubmed: 31630044
pii: S0169-5002(19)30679-8
doi: 10.1016/j.lungcan.2019.10.009
pii:
doi:
Substances chimiques
ARID1A protein, human
0
ARID1B protein, human
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
DNA-Binding Proteins
0
Nuclear Proteins
0
SMARCA2 protein, human
0
Transcription Factors
0
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-42Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.