Cargando…

Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment

Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tum...

Descripción completa

Detalles Bibliográficos
Autores principales: Xue, Xin-miao, Liu, Yu-yang, Chen, Xue-min, Tao, Bing-yan, Liu, Peng, Zhou, Han-wen, Zhang, Chi, Wang, Li, Jiang, Yu-ke, Ding, Zhi-wei, Shen, Wei-dong, Zhang, Jun, Yang, Shi-ming, Wang, Fang-yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768042/
https://www.ncbi.nlm.nih.gov/pubmed/36569293
http://dx.doi.org/10.3389/fphar.2022.1064032
_version_ 1784854089063989248
author Xue, Xin-miao
Liu, Yu-yang
Chen, Xue-min
Tao, Bing-yan
Liu, Peng
Zhou, Han-wen
Zhang, Chi
Wang, Li
Jiang, Yu-ke
Ding, Zhi-wei
Shen, Wei-dong
Zhang, Jun
Yang, Shi-ming
Wang, Fang-yuan
author_facet Xue, Xin-miao
Liu, Yu-yang
Chen, Xue-min
Tao, Bing-yan
Liu, Peng
Zhou, Han-wen
Zhang, Chi
Wang, Li
Jiang, Yu-ke
Ding, Zhi-wei
Shen, Wei-dong
Zhang, Jun
Yang, Shi-ming
Wang, Fang-yuan
author_sort Xue, Xin-miao
collection PubMed
description Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tumors. However, the prognostic significance of NT5E in pan-cancer is obscure so far. Methods: We explored the expression level of NT5E in cancers and adjacent tissues and revealed the relationship between the NT5E expression level and clinical outcomes in pan-cancer by utilizing the UCSC Xena database. Then, correlation analyses were performed to evaluate the relationship between NT5E expression and immune infiltration level via EPIC, MCP-counter and CIBERSORT methods, and the enrichment analysis were employed to identify NT5E-interacting molecules and functional pathways. Furthermore, we conducted single-cell analysis to explore the potential role of NT5E on single-cell level based on the CancerSEA database. Meanwhile, gene set enrichment analysis (GSEA) in single-cell level was also conducted in TISCH database and single-cell signature explorer was utilized to evaluate the epithelial-mesenchymal transition (EMT) level in each cell type. Results: The expression level of NT5E was aberrant in almost all cancer types, and was correlated with worse prognosis in several cancers. Notably, NT5E overexpression was related to worse overall survival (OS) in pancreatic adenocarcinoma (PAAD), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), stomach adenocarcinoma (STAD), uveal melanoma (UVM) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (p < 0.01). NT5E-related immune microenvironment analysis revealed that NT5E is associated positively with the degree of infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells in most cancers. Enrichment analysis of cellular component (CC) demonstrated the critical part of NT5E played in cell-substrate junction, cell-substrate adherens junction, focal adhesion and external side of plasma membrane. Finally, single-cell analysis of NT5E illuminated that EMT function of CAFs was elevated in basal cell carcinoma (BCC), skin cutaneous melanoma (SKCM), HNSC and PAAD. Conclusion: NT5E could serve as a potential prognostic biomarker for cancers. The potential mechanism may be related to the upregulated EMT function of CAFs, which provides novel inspiration for immunotherapy by targeting CAFs with high NT5E expression.
format Online
Article
Text
id pubmed-9768042
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-97680422022-12-22 Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment Xue, Xin-miao Liu, Yu-yang Chen, Xue-min Tao, Bing-yan Liu, Peng Zhou, Han-wen Zhang, Chi Wang, Li Jiang, Yu-ke Ding, Zhi-wei Shen, Wei-dong Zhang, Jun Yang, Shi-ming Wang, Fang-yuan Front Pharmacol Pharmacology Background: Ecto-5′-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tumors. However, the prognostic significance of NT5E in pan-cancer is obscure so far. Methods: We explored the expression level of NT5E in cancers and adjacent tissues and revealed the relationship between the NT5E expression level and clinical outcomes in pan-cancer by utilizing the UCSC Xena database. Then, correlation analyses were performed to evaluate the relationship between NT5E expression and immune infiltration level via EPIC, MCP-counter and CIBERSORT methods, and the enrichment analysis were employed to identify NT5E-interacting molecules and functional pathways. Furthermore, we conducted single-cell analysis to explore the potential role of NT5E on single-cell level based on the CancerSEA database. Meanwhile, gene set enrichment analysis (GSEA) in single-cell level was also conducted in TISCH database and single-cell signature explorer was utilized to evaluate the epithelial-mesenchymal transition (EMT) level in each cell type. Results: The expression level of NT5E was aberrant in almost all cancer types, and was correlated with worse prognosis in several cancers. Notably, NT5E overexpression was related to worse overall survival (OS) in pancreatic adenocarcinoma (PAAD), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), stomach adenocarcinoma (STAD), uveal melanoma (UVM) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) (p < 0.01). NT5E-related immune microenvironment analysis revealed that NT5E is associated positively with the degree of infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells in most cancers. Enrichment analysis of cellular component (CC) demonstrated the critical part of NT5E played in cell-substrate junction, cell-substrate adherens junction, focal adhesion and external side of plasma membrane. Finally, single-cell analysis of NT5E illuminated that EMT function of CAFs was elevated in basal cell carcinoma (BCC), skin cutaneous melanoma (SKCM), HNSC and PAAD. Conclusion: NT5E could serve as a potential prognostic biomarker for cancers. The potential mechanism may be related to the upregulated EMT function of CAFs, which provides novel inspiration for immunotherapy by targeting CAFs with high NT5E expression. Frontiers Media S.A. 2022-12-07 /pmc/articles/PMC9768042/ /pubmed/36569293 http://dx.doi.org/10.3389/fphar.2022.1064032 Text en Copyright © 2022 Xue, Liu, Chen, Tao, Liu, Zhou, Zhang, Wang, Jiang, Ding, Shen, Zhang, Yang 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 Pharmacology
Xue, Xin-miao
Liu, Yu-yang
Chen, Xue-min
Tao, Bing-yan
Liu, Peng
Zhou, Han-wen
Zhang, Chi
Wang, Li
Jiang, Yu-ke
Ding, Zhi-wei
Shen, Wei-dong
Zhang, Jun
Yang, Shi-ming
Wang, Fang-yuan
Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title_full Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title_fullStr Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title_full_unstemmed Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title_short Pan-cancer analysis identifies NT5E as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
title_sort pan-cancer analysis identifies nt5e as a novel prognostic biomarker on cancer-associated fibroblasts associated with unique tumor microenvironment
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768042/
https://www.ncbi.nlm.nih.gov/pubmed/36569293
http://dx.doi.org/10.3389/fphar.2022.1064032
work_keys_str_mv AT xuexinmiao pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT liuyuyang pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT chenxuemin pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT taobingyan pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT liupeng pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT zhouhanwen pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT zhangchi pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT wangli pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT jiangyuke pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT dingzhiwei pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT shenweidong pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT zhangjun pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT yangshiming pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment
AT wangfangyuan pancanceranalysisidentifiesnt5easanovelprognosticbiomarkeroncancerassociatedfibroblastsassociatedwithuniquetumormicroenvironment