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MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have shown promising results for the treatment of multiple cancers. ICIs and related therapies may also be useful for the treatment of thyroid cancer (TC). In TC, Myc binding protein 2 (MYCBP2) is correlated with inflammatory cell infiltration and ca...

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Autores principales: Wang, Guilin, Miao, Chen, Mo, Lijun, Kahlert, Ulf D., Wu, Jinfeng, Ou, Minglin, Huang, Renxiang, Feng, Ruifa, Pang, Weiyi, Shi, Wenjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792662/
https://www.ncbi.nlm.nih.gov/pubmed/36582246
http://dx.doi.org/10.3389/fimmu.2022.1048503
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author Wang, Guilin
Miao, Chen
Mo, Lijun
Kahlert, Ulf D.
Wu, Jinfeng
Ou, Minglin
Huang, Renxiang
Feng, Ruifa
Pang, Weiyi
Shi, Wenjie
author_facet Wang, Guilin
Miao, Chen
Mo, Lijun
Kahlert, Ulf D.
Wu, Jinfeng
Ou, Minglin
Huang, Renxiang
Feng, Ruifa
Pang, Weiyi
Shi, Wenjie
author_sort Wang, Guilin
collection PubMed
description INTRODUCTION: Immune checkpoint inhibitors (ICIs) have shown promising results for the treatment of multiple cancers. ICIs and related therapies may also be useful for the treatment of thyroid cancer (TC). In TC, Myc binding protein 2 (MYCBP2) is correlated with inflammatory cell infiltration and cancer prognosis. However, the relationship between MYCBP2 expression and ICI efficacy in TC patients is unclear. METHODS: We downloaded data from two TC cohorts, including transcriptomic data and clinical prognosis data. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict the efficacy of ICIs in TC patients. MCPcounter, xCell, and quanTIseq were used to calculate immune cell infiltration scores. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to evaluate signaling pathway scores. Immunohistochemical (IHC) analysis and clinical follow up was used to identify the MYCBP2 protein expression status in patients and associated with clinical outcome. RESULTS: A higher proportion of MYCBP2-high TC patients were predicted ICI responders than MYCBP2-low patients. MYCBP2-high patients also had significantly increased infiltration of CD8+ T cells, cytotoxic lymphocytes (CTLs), B cells, natural killer (NK) cells and dendritic cells (DC)s. Compared with MYCBP2-low patients, MYCBP2-high patients had higher expression of genes associated with B cells, CD8+ T cells, macrophages, plasmacytoid dendritic cells (pDCs), antigen processing and presentation, inflammatory stimulation, and interferon (IFN) responses. GSEA and ssGSEA also showed that MYCBP2-high patients had significantly increased activity of inflammatory factors and signaling pathways associated with immune responses.In addiation, Patients in our local cohort with high MYCBP2 expression always had a better prognosis and greater sensitivity to therapy while compared to patients with low MYCBP2 expression after six months clinic follow up. CONCLUSIONS: In this study, we found that MYCBP2 may be a predictive biomarker for ICI efficacy in TC patients. High MYCBP2 expression was associated with significantly enriched immune cell infiltration. MYCBP2 may also be involved in the regulation of signaling pathways associated with anti-tumor immune responses or the production of inflammatory factors.
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spelling pubmed-97926622022-12-28 MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients Wang, Guilin Miao, Chen Mo, Lijun Kahlert, Ulf D. Wu, Jinfeng Ou, Minglin Huang, Renxiang Feng, Ruifa Pang, Weiyi Shi, Wenjie Front Immunol Immunology INTRODUCTION: Immune checkpoint inhibitors (ICIs) have shown promising results for the treatment of multiple cancers. ICIs and related therapies may also be useful for the treatment of thyroid cancer (TC). In TC, Myc binding protein 2 (MYCBP2) is correlated with inflammatory cell infiltration and cancer prognosis. However, the relationship between MYCBP2 expression and ICI efficacy in TC patients is unclear. METHODS: We downloaded data from two TC cohorts, including transcriptomic data and clinical prognosis data. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict the efficacy of ICIs in TC patients. MCPcounter, xCell, and quanTIseq were used to calculate immune cell infiltration scores. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to evaluate signaling pathway scores. Immunohistochemical (IHC) analysis and clinical follow up was used to identify the MYCBP2 protein expression status in patients and associated with clinical outcome. RESULTS: A higher proportion of MYCBP2-high TC patients were predicted ICI responders than MYCBP2-low patients. MYCBP2-high patients also had significantly increased infiltration of CD8+ T cells, cytotoxic lymphocytes (CTLs), B cells, natural killer (NK) cells and dendritic cells (DC)s. Compared with MYCBP2-low patients, MYCBP2-high patients had higher expression of genes associated with B cells, CD8+ T cells, macrophages, plasmacytoid dendritic cells (pDCs), antigen processing and presentation, inflammatory stimulation, and interferon (IFN) responses. GSEA and ssGSEA also showed that MYCBP2-high patients had significantly increased activity of inflammatory factors and signaling pathways associated with immune responses.In addiation, Patients in our local cohort with high MYCBP2 expression always had a better prognosis and greater sensitivity to therapy while compared to patients with low MYCBP2 expression after six months clinic follow up. CONCLUSIONS: In this study, we found that MYCBP2 may be a predictive biomarker for ICI efficacy in TC patients. High MYCBP2 expression was associated with significantly enriched immune cell infiltration. MYCBP2 may also be involved in the regulation of signaling pathways associated with anti-tumor immune responses or the production of inflammatory factors. Frontiers Media S.A. 2022-12-13 /pmc/articles/PMC9792662/ /pubmed/36582246 http://dx.doi.org/10.3389/fimmu.2022.1048503 Text en Copyright © 2022 Wang, Miao, Mo, Kahlert, Wu, Ou, Huang, Feng, Pang and Shi 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, Guilin
Miao, Chen
Mo, Lijun
Kahlert, Ulf D.
Wu, Jinfeng
Ou, Minglin
Huang, Renxiang
Feng, Ruifa
Pang, Weiyi
Shi, Wenjie
MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title_full MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title_fullStr MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title_full_unstemmed MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title_short MYCBP2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
title_sort mycbp2 expression correlated with inflammatory cell infiltration and prognosis immunotherapy in thyroid cancer patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792662/
https://www.ncbi.nlm.nih.gov/pubmed/36582246
http://dx.doi.org/10.3389/fimmu.2022.1048503
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