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Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing

BACKGROUND: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing an...

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Autores principales: Wang, Jian, Sun, Hong-Cun, Cao, Cheng, Hu, Jian-Dao, Qian, Jing, Jiang, Tao, Jiang, Wen-Bo, Zhou, Shao, Qiu, Xiao-Wen, Wang, Hong-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196046/
https://www.ncbi.nlm.nih.gov/pubmed/37213285
http://dx.doi.org/10.3389/fonc.2023.1136729
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author Wang, Jian
Sun, Hong-Cun
Cao, Cheng
Hu, Jian-Dao
Qian, Jing
Jiang, Tao
Jiang, Wen-Bo
Zhou, Shao
Qiu, Xiao-Wen
Wang, Hong-Li
author_facet Wang, Jian
Sun, Hong-Cun
Cao, Cheng
Hu, Jian-Dao
Qian, Jing
Jiang, Tao
Jiang, Wen-Bo
Zhou, Shao
Qiu, Xiao-Wen
Wang, Hong-Li
author_sort Wang, Jian
collection PubMed
description BACKGROUND: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. METHODS: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The “cellchat” R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. RESULTS: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. CONCLUSION: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.
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spelling pubmed-101960462023-05-20 Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing Wang, Jian Sun, Hong-Cun Cao, Cheng Hu, Jian-Dao Qian, Jing Jiang, Tao Jiang, Wen-Bo Zhou, Shao Qiu, Xiao-Wen Wang, Hong-Li Front Oncol Oncology BACKGROUND: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. METHODS: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The “cellchat” R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. RESULTS: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. CONCLUSION: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies. Frontiers Media S.A. 2023-05-05 /pmc/articles/PMC10196046/ /pubmed/37213285 http://dx.doi.org/10.3389/fonc.2023.1136729 Text en Copyright © 2023 Wang, Sun, Cao, Hu, Qian, Jiang, Jiang, Zhou, Qiu and Wang 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
Wang, Jian
Sun, Hong-Cun
Cao, Cheng
Hu, Jian-Dao
Qian, Jing
Jiang, Tao
Jiang, Wen-Bo
Zhou, Shao
Qiu, Xiao-Wen
Wang, Hong-Li
Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title_full Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title_fullStr Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title_full_unstemmed Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title_short Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing
title_sort identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk rna-sequencing
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196046/
https://www.ncbi.nlm.nih.gov/pubmed/37213285
http://dx.doi.org/10.3389/fonc.2023.1136729
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