Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma

Abstract Background Tongue squamous cell carcinoma (TSCC) is characterized by aggressive invasion and poor prognosis. Currently, immune checkpoint inhibitors may prolong overall survival compared with conventional treatments. However, PD1/PDL1 remain inapplicable in predicting the prognosis of TSCC;...

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Autores principales:	Yi Jin, Zhanwang Wang, Dong He, Yuxing Zhu, Xingyu Chen, Ke Cao
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	CIBERSORT ESTIMATE LASSO PGK1 ssGSEA tongue squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/29b53b3198b14d458a8d32bfc09ae0f3
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spelling	oai:doaj.org-article:29b53b3198b14d458a8d32bfc09ae0f32021-12-01T04:49:16ZIdentification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma2045-763410.1002/cam4.4341https://doaj.org/article/29b53b3198b14d458a8d32bfc09ae0f32021-12-01T00:00:00Zhttps://doi.org/10.1002/cam4.4341https://doaj.org/toc/2045-7634Abstract Background Tongue squamous cell carcinoma (TSCC) is characterized by aggressive invasion and poor prognosis. Currently, immune checkpoint inhibitors may prolong overall survival compared with conventional treatments. However, PD1/PDL1 remain inapplicable in predicting the prognosis of TSCC; thus, it is urgent to explore the genetic characteristics of TSCC. Materials and methods We utilized single‐sample gene set enrichment analysis (ssGSEA) to classify TSCC patients from the TCGA database into clusters with different immune cell infiltrations. ESTIMATE (immune‐related scores) and CIBERSORT (immune cell distribution) analyses were used to evaluate the immune landscape among clusters. GO, KEGG, and GSEA analyses were performed to analyze the different underlying molecular mechanisms in the clusters. Based on the immune characteristics, we applied the LASSO Cox regression to select hub genes and construct a prognostic risk model. Finally, we established an interactive network among these hub genes by using Cytoscape, and a pan‐cancer analysis to further verify and decipher the innate function of these genes. Results Using ssGSEA, we constructed three functional clusters with different overall survival and immune‐cell infiltration. ESTIMATE and CIBERSORT analyses revealed the different distributions of immune cells (T cells, B cells, and macrophages) with diverse immune‐related scores (ESTIMATE, immune, stromal, and tumor purity scores). Moreover, pathways including those of the interferon‐gamma response, hypoxia, and glycolysis of the different subtypes were investigated to elucidate their involvement in mediating the heterogeneous immune characteristics. Subsequently, after LASSO Cox regression, a signature of 15 immune‐related genes was established that is more prognostically effective than the TNM stage. Furthermore, three hub genes—PGK1, GPI, and RPE—were selected using Cytoscape evaluation and verified by immunohistochemistry. PGK1, the foremost regulator, was a comprehensively profiled pan‐cancer, and a PGK1‐based interactive network was established. Conclusion Our results suggest that immune‐related genes and clusters in TSCC have the potential to guide individualized treatments.Yi JinZhanwang WangDong HeYuxing ZhuXingyu ChenKe CaoWileyarticleCIBERSORTESTIMATELASSOPGK1ssGSEAtongue squamous cell carcinomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 23, Pp 8693-8707 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CIBERSORT ESTIMATE LASSO PGK1 ssGSEA tongue squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	CIBERSORT ESTIMATE LASSO PGK1 ssGSEA tongue squamous cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yi Jin Zhanwang Wang Dong He Yuxing Zhu Xingyu Chen Ke Cao Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
description	Abstract Background Tongue squamous cell carcinoma (TSCC) is characterized by aggressive invasion and poor prognosis. Currently, immune checkpoint inhibitors may prolong overall survival compared with conventional treatments. However, PD1/PDL1 remain inapplicable in predicting the prognosis of TSCC; thus, it is urgent to explore the genetic characteristics of TSCC. Materials and methods We utilized single‐sample gene set enrichment analysis (ssGSEA) to classify TSCC patients from the TCGA database into clusters with different immune cell infiltrations. ESTIMATE (immune‐related scores) and CIBERSORT (immune cell distribution) analyses were used to evaluate the immune landscape among clusters. GO, KEGG, and GSEA analyses were performed to analyze the different underlying molecular mechanisms in the clusters. Based on the immune characteristics, we applied the LASSO Cox regression to select hub genes and construct a prognostic risk model. Finally, we established an interactive network among these hub genes by using Cytoscape, and a pan‐cancer analysis to further verify and decipher the innate function of these genes. Results Using ssGSEA, we constructed three functional clusters with different overall survival and immune‐cell infiltration. ESTIMATE and CIBERSORT analyses revealed the different distributions of immune cells (T cells, B cells, and macrophages) with diverse immune‐related scores (ESTIMATE, immune, stromal, and tumor purity scores). Moreover, pathways including those of the interferon‐gamma response, hypoxia, and glycolysis of the different subtypes were investigated to elucidate their involvement in mediating the heterogeneous immune characteristics. Subsequently, after LASSO Cox regression, a signature of 15 immune‐related genes was established that is more prognostically effective than the TNM stage. Furthermore, three hub genes—PGK1, GPI, and RPE—were selected using Cytoscape evaluation and verified by immunohistochemistry. PGK1, the foremost regulator, was a comprehensively profiled pan‐cancer, and a PGK1‐based interactive network was established. Conclusion Our results suggest that immune‐related genes and clusters in TSCC have the potential to guide individualized treatments.
format	article
author	Yi Jin Zhanwang Wang Dong He Yuxing Zhu Xingyu Chen Ke Cao
author_facet	Yi Jin Zhanwang Wang Dong He Yuxing Zhu Xingyu Chen Ke Cao
author_sort	Yi Jin
title	Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
title_short	Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
title_full	Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
title_fullStr	Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
title_full_unstemmed	Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
title_sort	identification of novel subtypes based on ssgsea in immune‐related prognostic signature for tongue squamous cell carcinoma
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/29b53b3198b14d458a8d32bfc09ae0f3
work_keys_str_mv	AT yijin identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma AT zhanwangwang identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma AT donghe identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma AT yuxingzhu identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma AT xingyuchen identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma AT kecao identificationofnovelsubtypesbasedonssgseainimmunerelatedprognosticsignaturefortonguesquamouscellcarcinoma
_version_	1718405715249332224

Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma

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