Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma

Background. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials...

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Main Authors: Chen Zou, Dahong Huang, Haigang Wei, Siyuan Wu, Jing Song, Zhe Tang, Xia Li, Yilong Ai
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/6203759
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author Chen Zou
Dahong Huang
Haigang Wei
Siyuan Wu
Jing Song
Zhe Tang
Xia Li
Yilong Ai
author_facet Chen Zou
Dahong Huang
Haigang Wei
Siyuan Wu
Jing Song
Zhe Tang
Xia Li
Yilong Ai
author_sort Chen Zou
collection DOAJ
description Background. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods. Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results. In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion. In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.
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spelling doaj-art-b4d606fbe75f4fa7bdaf20c3befcc9782025-08-20T03:39:22ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/62037596203759Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell CarcinomaChen Zou0Dahong Huang1Haigang Wei2Siyuan Wu3Jing Song4Zhe Tang5Xia Li6Yilong Ai7Foshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaFoshan Stomatological Hospital, School of Medicine, Foshan University, Foshan, Guangdong, ChinaBackground. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods. Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results. In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion. In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.http://dx.doi.org/10.1155/2021/6203759
spellingShingle Chen Zou
Dahong Huang
Haigang Wei
Siyuan Wu
Jing Song
Zhe Tang
Xia Li
Yilong Ai
Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
Journal of Immunology Research
title Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
title_full Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
title_fullStr Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
title_full_unstemmed Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
title_short Identification of Immune-Related Risk Signatures for the Prognostic Prediction in Oral Squamous Cell Carcinoma
title_sort identification of immune related risk signatures for the prognostic prediction in oral squamous cell carcinoma
url http://dx.doi.org/10.1155/2021/6203759
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