Cargando…
The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
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 instabi...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822341/ https://www.ncbi.nlm.nih.gov/pubmed/33481850 http://dx.doi.org/10.1371/journal.pone.0245356 |
_version_ | 1783639612983345152 |
---|---|
author | Huang, Shih-Chiang Ng, Kwai-Fong Chang, Ian Yi-Feng Chang, Chee-Jen Chao, Yi-Chun Chang, Shu-Chen Chen, Min-Chi Yeh, Ta-Sen Chen, Tse-Ching |
author_facet | Huang, Shih-Chiang Ng, Kwai-Fong Chang, Ian Yi-Feng Chang, Chee-Jen Chao, Yi-Chun Chang, Shu-Chen Chen, Min-Chi Yeh, Ta-Sen Chen, Tse-Ching |
author_sort | Huang, Shih-Chiang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7822341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78223412021-01-29 The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes Huang, Shih-Chiang Ng, Kwai-Fong Chang, Ian Yi-Feng Chang, Chee-Jen Chao, Yi-Chun Chang, Shu-Chen Chen, Min-Chi Yeh, Ta-Sen Chen, Tse-Ching PLoS One Research Article 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. Public Library of Science 2021-01-22 /pmc/articles/PMC7822341/ /pubmed/33481850 http://dx.doi.org/10.1371/journal.pone.0245356 Text en © 2021 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Huang, Shih-Chiang Ng, Kwai-Fong Chang, Ian Yi-Feng Chang, Chee-Jen Chao, Yi-Chun Chang, Shu-Chen Chen, Min-Chi Yeh, Ta-Sen Chen, Tse-Ching The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title | The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title_full | The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title_fullStr | The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title_full_unstemmed | The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title_short | The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes |
title_sort | clinicopathological significance of swi/snf alterations in gastric cancer is associated with the molecular subtypes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822341/ https://www.ncbi.nlm.nih.gov/pubmed/33481850 http://dx.doi.org/10.1371/journal.pone.0245356 |
work_keys_str_mv | AT huangshihchiang theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT ngkwaifong theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changianyifeng theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changcheejen theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chaoyichun theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changshuchen theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chenminchi theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT yehtasen theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chentseching theclinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT huangshihchiang clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT ngkwaifong clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changianyifeng clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changcheejen clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chaoyichun clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT changshuchen clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chenminchi clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT yehtasen clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes AT chentseching clinicopathologicalsignificanceofswisnfalterationsingastriccancerisassociatedwiththemolecularsubtypes |