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Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TI...

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Autores principales: Wang, Gaoming, Yang, Ludi, Wang, Yongkun, Hu, Renhao, Zhang, Kehui, Guo, Taohua, Chen, Bo, Jiang, Xiaohua, Cui, Ran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309259/
https://www.ncbi.nlm.nih.gov/pubmed/35898512
http://dx.doi.org/10.3389/fimmu.2022.939836
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author Wang, Gaoming
Yang, Ludi
Wang, Yongkun
Hu, Renhao
Zhang, Kehui
Guo, Taohua
Chen, Bo
Jiang, Xiaohua
Cui, Ran
author_facet Wang, Gaoming
Yang, Ludi
Wang, Yongkun
Hu, Renhao
Zhang, Kehui
Guo, Taohua
Chen, Bo
Jiang, Xiaohua
Cui, Ran
author_sort Wang, Gaoming
collection PubMed
description Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.
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spelling pubmed-93092592022-07-26 Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer Wang, Gaoming Yang, Ludi Wang, Yongkun Hu, Renhao Zhang, Kehui Guo, Taohua Chen, Bo Jiang, Xiaohua Cui, Ran Front Immunol Immunology Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9309259/ /pubmed/35898512 http://dx.doi.org/10.3389/fimmu.2022.939836 Text en Copyright © 2022 Wang, Yang, Wang, Hu, Zhang, Guo, Chen, Jiang and Cui 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 Immunology
Wang, Gaoming
Yang, Ludi
Wang, Yongkun
Hu, Renhao
Zhang, Kehui
Guo, Taohua
Chen, Bo
Jiang, Xiaohua
Cui, Ran
Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title_full Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title_fullStr Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title_full_unstemmed Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title_short Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
title_sort characterization of immune-related molecular subtypes and a prognostic signature correlating with the response to immunotherapy in patients with gastric cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309259/
https://www.ncbi.nlm.nih.gov/pubmed/35898512
http://dx.doi.org/10.3389/fimmu.2022.939836
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