In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 1 ( 2021-1-22), p. e0245356-
Abstract:
The clinicopathological significance of altered SWI/SNF complex has not been well evaluated in gastric cancer (GC). We examined SMARCA2, SMARCA4, SMARCB1 and ARID1A expression by immunohistochemistry in 1224 surgically resected GCs with subtyping into Epstein-Barr virus (EBV), microsatellite instability (MSI) and non-EBV/MSI Lauren histotypes. SWI/SNF mutations were investigated using the GC dataset of the TCGA Pan-Cancer Atlas. Clinicopathological association was assessed by statistical analysis. There were 427 cases (35%) of SWI/SNF-attenuated GC, including 344 SMARCA2 (28%), 28 SMARCA4 (2%), 11 SMARCB1 (1%) and 197 ARID1A (16%) cases. Simultaneous alterations of multiple subunits were observed. Compared to SWI/SNF-retained cases, SWI/SNF-attenuated GC exhibited a significant predilection to older ages, EBV and MSI genotypes, higher lymphatic invasion and less hematogenous recurrence ( P 〈 0.05). SWI/SNF attenuation was an independent risk factor for short overall survival ( P = 0.001, hazard ratio 1.360, 95% confidence interval 1.138–1.625). The survival impact stemmed from SMARCA2-attenuated GCs in stage III and non-EBV/MSI diffuse/mixed subtypes ( P = 0.019 and 〈 0.001, respectively). ARID1A-lost/heterogeneous GCs were more aggressive in the EBV genotype ( P = 0.016). SMARCB1 or SMARCA4 loss was not restricted to rhabdoid/undifferentiated carcinoma. In the TCGA dataset, 223 of 434 GCs (52%) harbored deleterious SWI/SNF mutations, including ARID1A (27%), SMARCA2 (9%), ARID2 (9%), ARID1B (8%), PBRM1 (7%), and SMARCA4 (7%). SWI/SNF-mutated GCs displayed a favorable outcome owing to the high percentage with the MSI genotype. In conclusion, SWI/SNF-altered GCs are common and the clinicopathological significance is related to the genotype.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0245356
DOI:
10.1371/journal.pone.0245356.g001
DOI:
10.1371/journal.pone.0245356.g002
DOI:
10.1371/journal.pone.0245356.g003
DOI:
10.1371/journal.pone.0245356.g004
DOI:
10.1371/journal.pone.0245356.t001
DOI:
10.1371/journal.pone.0245356.s001
DOI:
10.1371/journal.pone.0245356.s002
DOI:
10.1371/journal.pone.0245356.s003
DOI:
10.1371/journal.pone.0245356.s004
DOI:
10.1371/journal.pone.0245356.r001
DOI:
10.1371/journal.pone.0245356.r002
DOI:
10.1371/journal.pone.0245356.r003
DOI:
10.1371/journal.pone.0245356.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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