Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma
Hypoxia plays a critical role in head and neck squamous cell carcinoma (HNSCC) prognosis. However, till now, robust and reliable hypoxia-related prognostic signatures have not been established for an accurate prognostic evaluation in HNSCC patients. This article focused on establishing a risk score...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.943945/full |
| _version_ | 1811224985446907904 |
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| author | Su-Ran Li Qi-Wen Man Qi-Wen Man Bing Liu Bing Liu |
| author_facet | Su-Ran Li Qi-Wen Man Qi-Wen Man Bing Liu Bing Liu |
| author_sort | Su-Ran Li |
| collection | DOAJ |
| description | Hypoxia plays a critical role in head and neck squamous cell carcinoma (HNSCC) prognosis. However, till now, robust and reliable hypoxia-related prognostic signatures have not been established for an accurate prognostic evaluation in HNSCC patients. This article focused on establishing a risk score model to evaluate the prognosis and guide treatment for HNSCC patients. RNA-seq data and clinical information of 502 HNSCC patients and 44 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. 433 samples from three Gene Expression Omnibus (GEO) datasets were incorporated as an external validation cohort. In the training cohort, prognostic-related genes were screened and LASSO regression analyses were performed for signature establishment. A scoring system based on SRPX, PGK1, STG1, HS3ST1, CDKN1B, and HK1 showed an excellent prediction capacity for an overall prognosis for HNSCC patients. Patients were divided into high- and low-risk groups, and the survival status of the two groups exhibited a statistically significant difference. Subsequently, gene set enrichment analysis (GSEA) was carried out to explore the underlying mechanisms for the prognosis differences between the high- and low-risk groups. The tumor immune microenvironment was evaluated by CIBERSORT, ESTIMATE, TIDE, and xCell algorithm, etc. Then, we explored the relationships between this prognostic model and the levels of immune checkpoint-related genes. Cox regression analysis and nomogram plot indicated the scoring system was an independent predictor for HNSCC. Moreover, a comparison of predictive capability has been made between the present signature and existing prognostic signatures for HNSCC patients. Finally, we detected the expression levels of proteins encoded by six-HRGs via immunohistochemical analysis in tissue microarray. Collectively, a novel integrated signature considering both HRGs and clinicopathological parameters will serve as a prospective candidate for the prognostic evaluation of HNSCC patients. |
| first_indexed | 2024-04-12T08:58:10Z |
| format | Article |
| id | doaj.art-3fa42cfb1a814590a0114d6d6618f298 |
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| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T08:58:10Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-3fa42cfb1a814590a0114d6d6618f2982022-12-22T03:39:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.943945943945Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinomaSu-Ran Li0Qi-Wen Man1Qi-Wen Man2Bing Liu3Bing Liu4The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaDepartment of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, ChinaThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, ChinaDepartment of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, ChinaHypoxia plays a critical role in head and neck squamous cell carcinoma (HNSCC) prognosis. However, till now, robust and reliable hypoxia-related prognostic signatures have not been established for an accurate prognostic evaluation in HNSCC patients. This article focused on establishing a risk score model to evaluate the prognosis and guide treatment for HNSCC patients. RNA-seq data and clinical information of 502 HNSCC patients and 44 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. 433 samples from three Gene Expression Omnibus (GEO) datasets were incorporated as an external validation cohort. In the training cohort, prognostic-related genes were screened and LASSO regression analyses were performed for signature establishment. A scoring system based on SRPX, PGK1, STG1, HS3ST1, CDKN1B, and HK1 showed an excellent prediction capacity for an overall prognosis for HNSCC patients. Patients were divided into high- and low-risk groups, and the survival status of the two groups exhibited a statistically significant difference. Subsequently, gene set enrichment analysis (GSEA) was carried out to explore the underlying mechanisms for the prognosis differences between the high- and low-risk groups. The tumor immune microenvironment was evaluated by CIBERSORT, ESTIMATE, TIDE, and xCell algorithm, etc. Then, we explored the relationships between this prognostic model and the levels of immune checkpoint-related genes. Cox regression analysis and nomogram plot indicated the scoring system was an independent predictor for HNSCC. Moreover, a comparison of predictive capability has been made between the present signature and existing prognostic signatures for HNSCC patients. Finally, we detected the expression levels of proteins encoded by six-HRGs via immunohistochemical analysis in tissue microarray. Collectively, a novel integrated signature considering both HRGs and clinicopathological parameters will serve as a prospective candidate for the prognostic evaluation of HNSCC patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.943945/fullhead and neck squamous cell carcinomahypoxiaThe Cancer Genome AtlasGene Expression Omnibustumor microenvironmentprognostic signature |
| spellingShingle | Su-Ran Li Qi-Wen Man Qi-Wen Man Bing Liu Bing Liu Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma Frontiers in Oncology head and neck squamous cell carcinoma hypoxia The Cancer Genome Atlas Gene Expression Omnibus tumor microenvironment prognostic signature |
| title | Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| title_full | Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| title_fullStr | Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| title_full_unstemmed | Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| title_short | Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| title_sort | development and validation of a novel hypoxia related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma |
| topic | head and neck squamous cell carcinoma hypoxia The Cancer Genome Atlas Gene Expression Omnibus tumor microenvironment prognostic signature |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.943945/full |
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