Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma

Su-Ran Li; Qi-Wen Man; Bing Liu

doi:10.3389/fonc.2022.943945

Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma

Front Oncol. 2022 Nov 14:12:943945. doi: 10.3389/fonc.2022.943945. eCollection 2022.

Authors

Su-Ran Li¹, Qi-Wen Man^{1

2}, Bing Liu^{1

2}

Affiliations

¹ The 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, China.
² Department of Oral Maxillofacial Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.

Abstract

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.

Keywords: Gene Expression Omnibus; The Cancer Genome Atlas; head and neck squamous cell carcinoma; hypoxia; prognostic signature; tumor microenvironment.