Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma

The incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer an...

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Autores principales:	Jun Li, Yunhong Xu, Gang Peng, Kuikui Zhu, Zilong Wu, Liangliang Shi, Gang Wu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	nerve prognostic model HNSC neurotransmitter bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/a816d8c18e5f43ae91a43a9524c8f94d
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spelling	oai:doaj.org-article:a816d8c18e5f43ae91a43a9524c8f94d2021-12-01T11:23:12ZIdentification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma2234-943X10.3389/fonc.2021.788671https://doaj.org/article/a816d8c18e5f43ae91a43a9524c8f94d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.788671/fullhttps://doaj.org/toc/2234-943XThe incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer and pancreatic cancer. However, the role of cancer-nerve cross-talk-related genes (NCCGs) in HNSC is unclear. In our study, we constructed a prognostic model based on genes with prognostic value in NCCGs. We used Pearson’s correlation to analyze the relationship between NCCGs and immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. We used single-cell sequencing data to analyze the expression of genes associated with stage in different cells and explored the possible pathways affected by these genes via gene set enrichment analysis. In the TCGA-HNSC cohort, a total of 23 genes were up- or downregulated compared with normal tissues. GO and KEGG pathway analysis suggested that NCCGs are mainly concentrated in membrane potential regulation, chemical synapse, axon formation, and neuroreceptor-ligand interaction. Ten genes were identified as prognosis genes by Kaplan-Meier plotter and used as candidate genes for LASSO regression. We constructed a seven-gene prognostic model (NTRK1, L1CAM, GRIN3A, CHRNA5, CHRNA6, CHRNB4, CHRND). The model could effectively predict the 1-, 3-, and 5-year survival rates in the TCGA-HNSC cohort, and the effectiveness of the model was verified by external test data. The genes included in the model were significantly correlated with immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.Jun LiYunhong XuGang PengKuikui ZhuZilong WuLiangliang ShiGang WuFrontiers Media S.A.articlenerveprognostic modelHNSCneurotransmitterbioinformaticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nerve prognostic model HNSC neurotransmitter bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	nerve prognostic model HNSC neurotransmitter bioinformatics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jun Li Yunhong Xu Gang Peng Kuikui Zhu Zilong Wu Liangliang Shi Gang Wu Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
description	The incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer and pancreatic cancer. However, the role of cancer-nerve cross-talk-related genes (NCCGs) in HNSC is unclear. In our study, we constructed a prognostic model based on genes with prognostic value in NCCGs. We used Pearson’s correlation to analyze the relationship between NCCGs and immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. We used single-cell sequencing data to analyze the expression of genes associated with stage in different cells and explored the possible pathways affected by these genes via gene set enrichment analysis. In the TCGA-HNSC cohort, a total of 23 genes were up- or downregulated compared with normal tissues. GO and KEGG pathway analysis suggested that NCCGs are mainly concentrated in membrane potential regulation, chemical synapse, axon formation, and neuroreceptor-ligand interaction. Ten genes were identified as prognosis genes by Kaplan-Meier plotter and used as candidate genes for LASSO regression. We constructed a seven-gene prognostic model (NTRK1, L1CAM, GRIN3A, CHRNA5, CHRNA6, CHRNB4, CHRND). The model could effectively predict the 1-, 3-, and 5-year survival rates in the TCGA-HNSC cohort, and the effectiveness of the model was verified by external test data. The genes included in the model were significantly correlated with immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.
format	article
author	Jun Li Yunhong Xu Gang Peng Kuikui Zhu Zilong Wu Liangliang Shi Gang Wu
author_facet	Jun Li Yunhong Xu Gang Peng Kuikui Zhu Zilong Wu Liangliang Shi Gang Wu
author_sort	Jun Li
title	Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
title_short	Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
title_full	Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
title_fullStr	Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed	Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma
title_sort	identification of the nerve-cancer cross-talk-related prognostic gene model in head and neck squamous cell carcinoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a816d8c18e5f43ae91a43a9524c8f94d
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Identification of the Nerve-Cancer Cross-Talk-Related Prognostic Gene Model in Head and Neck Squamous Cell Carcinoma

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