AUTHOR=Li Su-Ran , Man Qi-Wen , Liu Bing 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.943945

DOI=10.3389/fonc.2022.943945

ISSN=2234-943X

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 prognosis evaluation in HNSCC patients. This article focused on establishing a risk score model to evaluate the prognosis and guide treatment for HNSCC patients. 502 patients and 44 normal samples from The Cancer Genome Atlas (TCGA) and 433 samples from three Gene Expression Omnibus (GEO) datasets were incorporated as the training and validation cohort, respectively. 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 the high- and low-risk groups, and the survival status of the two groups exhibited a statistically significant difference. Subsequently, gene set enrichment analysis (GSEA) and the Gene Ontology (GO) enrichment analysis were carried out to explore the underlying mechanisms for the prognosis differences between the high- and low-risk groups. 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. 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 prognosis evaluation for HNSCC patients.