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Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy

Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic p...

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Autores principales: Xu, Feng, Chen, Jie-xin, Yang, Xiong-bin, Hong, Xin-bin, Li, Zi-xiong, Lin, Ling, Chen, Yong-song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183104/
https://www.ncbi.nlm.nih.gov/pubmed/32346613
http://dx.doi.org/10.1016/j.omto.2020.03.021
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author Xu, Feng
Chen, Jie-xin
Yang, Xiong-bin
Hong, Xin-bin
Li, Zi-xiong
Lin, Ling
Chen, Yong-song
author_facet Xu, Feng
Chen, Jie-xin
Yang, Xiong-bin
Hong, Xin-bin
Li, Zi-xiong
Lin, Ling
Chen, Yong-song
author_sort Xu, Feng
collection PubMed
description Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8(+) T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFNγ) gene signature were also observed in the Immunity High subtype. N(6)-methyladenosine (m(6)A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancer-associated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment.
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spelling pubmed-71831042020-04-28 Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy Xu, Feng Chen, Jie-xin Yang, Xiong-bin Hong, Xin-bin Li, Zi-xiong Lin, Ling Chen, Yong-song Mol Ther Oncolytics Article Lung cancer is the most common cause of cancer deaths worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. However, the prognostic and predictive outcomes differ because of this cancer type heterogeneity. LUAD subtypes were identified on the basis of the immunogenomic profiling of 29 immune signatures. We named three LUAD subtypes: Immunity High, Immunity Medium, and Immunity Low. The Immunity High subtype was characterized by immune activation, e.g., increased immune scores, elevated stromal scores and the highest infiltration of CD8(+) T cells, and decreased tumor purities. Activated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T helper 1 (Th1)/interferon-gamma (IFNγ) gene signature were also observed in the Immunity High subtype. N(6)-methyladenosine (m(6)A) RNA methylation, associated with cancer initiation and progression, was reduced in the Immunity High subtype. Functional and signaling pathway enrichment analysis further showed that differentially expressed genes between the Immunity High subtype and the other subtypes mainly participated in immune response and some cancer-associated pathways. In addition, the Immunity High subtype exhibited more sensitivity to immunotherapy and chemotherapy. Finally, candidate compounds that aimed at LUAD subtype differentiation were identified. Comprehensively characterizing the LUAD subtypes based on immune signatures may help to provide potential strategies for LUAD treatment. American Society of Gene & Cell Therapy 2020-04-07 /pmc/articles/PMC7183104/ /pubmed/32346613 http://dx.doi.org/10.1016/j.omto.2020.03.021 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Feng
Chen, Jie-xin
Yang, Xiong-bin
Hong, Xin-bin
Li, Zi-xiong
Lin, Ling
Chen, Yong-song
Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title_full Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title_fullStr Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title_full_unstemmed Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title_short Analysis of Lung Adenocarcinoma Subtypes Based on Immune Signatures Identifies Clinical Implications for Cancer Therapy
title_sort analysis of lung adenocarcinoma subtypes based on immune signatures identifies clinical implications for cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183104/
https://www.ncbi.nlm.nih.gov/pubmed/32346613
http://dx.doi.org/10.1016/j.omto.2020.03.021
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