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A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer

Objective: Gastric cancer (GC) is a highly heterogeneous malignant carcinoma. This study aimed to conduct an exosome-based classification for assisting personalized therapy for GC. Methods: Based on the expression profiling of prognostic exosome-related genes, GC patients in The Cancer Genome Atlas...

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Autores principales: Lin, Yubiao, Huang, Kaida, Cai, Zhezhen, Chen, Yide, Feng, Lihua, Gao, Yingqin, Zheng, Wenhui, Fan, Xin, Qiu, Guoqin, Zhuang, Jianmin, Feng, Shuitu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204030/
https://www.ncbi.nlm.nih.gov/pubmed/35721114
http://dx.doi.org/10.3389/fphar.2022.884090
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author Lin, Yubiao
Huang, Kaida
Cai, Zhezhen
Chen, Yide
Feng, Lihua
Gao, Yingqin
Zheng, Wenhui
Fan, Xin
Qiu, Guoqin
Zhuang, Jianmin
Feng, Shuitu
author_facet Lin, Yubiao
Huang, Kaida
Cai, Zhezhen
Chen, Yide
Feng, Lihua
Gao, Yingqin
Zheng, Wenhui
Fan, Xin
Qiu, Guoqin
Zhuang, Jianmin
Feng, Shuitu
author_sort Lin, Yubiao
collection PubMed
description Objective: Gastric cancer (GC) is a highly heterogeneous malignant carcinoma. This study aimed to conduct an exosome-based classification for assisting personalized therapy for GC. Methods: Based on the expression profiling of prognostic exosome-related genes, GC patients in The Cancer Genome Atlas (TCGA) cohort were classified using the unsupervised consensus clustering approach, and the reproducibility of this classification was confirmed in the GSE84437 cohort. An exosome-based gene signature was developed via Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Immunological features, responses to immune checkpoint inhibitors, and genetic alterations were evaluated via computational methods. Results: Two exosome-relevant phenotypes (A and B) were clustered, and this classification was independent of immune subtypes and TCGA subtypes. Exosome-relevant phenotype B had a poorer prognosis and an inflamed tumor microenvironment (TME) relative to phenotype A. Patients with phenotype B presented higher responses to the anti-CTLA4 inhibitor. Moreover, phenotype B occurred at a higher frequency of genetic mutation than phenotype A. The exosome-based gene signature (GPX3, RGS2, MATN3, SLC7A2, and SNCG) could independently and accurately predict GC prognosis, which was linked to stromal activation and immunosuppression. Conclusion: Our findings offer a conceptual frame to further comprehend the roles of exosomes in immune escape mechanisms and genomic alterations of GC. More work is required to evaluate the reference value of exosome-relevant phenotypes for designing immunotherapeutic regimens.
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spelling pubmed-92040302022-06-18 A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer Lin, Yubiao Huang, Kaida Cai, Zhezhen Chen, Yide Feng, Lihua Gao, Yingqin Zheng, Wenhui Fan, Xin Qiu, Guoqin Zhuang, Jianmin Feng, Shuitu Front Pharmacol Pharmacology Objective: Gastric cancer (GC) is a highly heterogeneous malignant carcinoma. This study aimed to conduct an exosome-based classification for assisting personalized therapy for GC. Methods: Based on the expression profiling of prognostic exosome-related genes, GC patients in The Cancer Genome Atlas (TCGA) cohort were classified using the unsupervised consensus clustering approach, and the reproducibility of this classification was confirmed in the GSE84437 cohort. An exosome-based gene signature was developed via Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Immunological features, responses to immune checkpoint inhibitors, and genetic alterations were evaluated via computational methods. Results: Two exosome-relevant phenotypes (A and B) were clustered, and this classification was independent of immune subtypes and TCGA subtypes. Exosome-relevant phenotype B had a poorer prognosis and an inflamed tumor microenvironment (TME) relative to phenotype A. Patients with phenotype B presented higher responses to the anti-CTLA4 inhibitor. Moreover, phenotype B occurred at a higher frequency of genetic mutation than phenotype A. The exosome-based gene signature (GPX3, RGS2, MATN3, SLC7A2, and SNCG) could independently and accurately predict GC prognosis, which was linked to stromal activation and immunosuppression. Conclusion: Our findings offer a conceptual frame to further comprehend the roles of exosomes in immune escape mechanisms and genomic alterations of GC. More work is required to evaluate the reference value of exosome-relevant phenotypes for designing immunotherapeutic regimens. Frontiers Media S.A. 2022-06-03 /pmc/articles/PMC9204030/ /pubmed/35721114 http://dx.doi.org/10.3389/fphar.2022.884090 Text en Copyright © 2022 Lin, Huang, Cai, Chen, Feng, Gao, Zheng, Fan, Qiu, Zhuang and Feng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lin, Yubiao
Huang, Kaida
Cai, Zhezhen
Chen, Yide
Feng, Lihua
Gao, Yingqin
Zheng, Wenhui
Fan, Xin
Qiu, Guoqin
Zhuang, Jianmin
Feng, Shuitu
A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title_full A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title_fullStr A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title_full_unstemmed A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title_short A Novel Exosome-Relevant Molecular Classification Uncovers Distinct Immune Escape Mechanisms and Genomic Alterations in Gastric Cancer
title_sort novel exosome-relevant molecular classification uncovers distinct immune escape mechanisms and genomic alterations in gastric cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204030/
https://www.ncbi.nlm.nih.gov/pubmed/35721114
http://dx.doi.org/10.3389/fphar.2022.884090
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