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Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF...

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Autores principales: Li, Xuejie, Liu, Zheqi, Zhou, Wenkai, Liu, Xiaofang, Cao, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364714/
https://www.ncbi.nlm.nih.gov/pubmed/34391381
http://dx.doi.org/10.1186/s12885-021-08671-1
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author Li, Xuejie
Liu, Zheqi
Zhou, Wenkai
Liu, Xiaofang
Cao, Wei
author_facet Li, Xuejie
Liu, Zheqi
Zhou, Wenkai
Liu, Xiaofang
Cao, Wei
author_sort Li, Xuejie
collection PubMed
description OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. RESULTS: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. CONCLUSION: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08671-1.
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spelling pubmed-83647142021-08-17 Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome Li, Xuejie Liu, Zheqi Zhou, Wenkai Liu, Xiaofang Cao, Wei BMC Cancer Research OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. RESULTS: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. CONCLUSION: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08671-1. BioMed Central 2021-08-15 /pmc/articles/PMC8364714/ /pubmed/34391381 http://dx.doi.org/10.1186/s12885-021-08671-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Xuejie
Liu, Zheqi
Zhou, Wenkai
Liu, Xiaofang
Cao, Wei
Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title_full Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title_fullStr Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title_full_unstemmed Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title_short Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome
title_sort downregulation of ccl22 and mutated notch1 in tongue and mouth floor squamous cell carcinoma results in decreased th2 cell recruitment and expression, predicting poor clinical outcome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364714/
https://www.ncbi.nlm.nih.gov/pubmed/34391381
http://dx.doi.org/10.1186/s12885-021-08671-1
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