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Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy
BACKGROUND: Recently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis. METHODS: Based on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892447/ https://www.ncbi.nlm.nih.gov/pubmed/36741716 http://dx.doi.org/10.3389/fonc.2022.1118472 |
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author | Chen, Can Chen, Lin-Yuan Yang, Rui-Xia Zhang, Jie-Xin Shao, Peng-Fei Xu, Hua-Guo |
author_facet | Chen, Can Chen, Lin-Yuan Yang, Rui-Xia Zhang, Jie-Xin Shao, Peng-Fei Xu, Hua-Guo |
author_sort | Chen, Can |
collection | PubMed |
description | BACKGROUND: Recently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis. METHODS: Based on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients. RESULTS: We proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines. CONCLUSIONS: Evaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment. |
format | Online Article Text |
id | pubmed-9892447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98924472023-02-03 Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy Chen, Can Chen, Lin-Yuan Yang, Rui-Xia Zhang, Jie-Xin Shao, Peng-Fei Xu, Hua-Guo Front Oncol Oncology BACKGROUND: Recently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis. METHODS: Based on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients. RESULTS: We proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines. CONCLUSIONS: Evaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment. Frontiers Media S.A. 2023-01-19 /pmc/articles/PMC9892447/ /pubmed/36741716 http://dx.doi.org/10.3389/fonc.2022.1118472 Text en Copyright © 2023 Chen, Chen, Yang, Zhang, Shao and Xu 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 | Oncology Chen, Can Chen, Lin-Yuan Yang, Rui-Xia Zhang, Jie-Xin Shao, Peng-Fei Xu, Hua-Guo Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title | Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title_full | Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title_fullStr | Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title_full_unstemmed | Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title_short | Identification of IRF-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
title_sort | identification of irf-associated molecular subtypes in clear cell renal cell carcinoma to characterize immunological characteristics and guide therapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892447/ https://www.ncbi.nlm.nih.gov/pubmed/36741716 http://dx.doi.org/10.3389/fonc.2022.1118472 |
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