Hypoxia-related signature to risk stratify patients for the benefit of immune checkpoint inhibitors therapy in head and neck squamous cell carcinoma: An experimental study

• Published in: Medicine (Baltimore) 2024-08, Vol.103 (31), p.e39184
• Main Authors: Zhao, Yuemei, Yang, Zhe, Fu, Min, Wu, Shuang, Wang, Mingyu, Li, Jinglong, Wang, Zhanqiu, Li, Wenfei
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers, Tumor - genetics; Clinical Trial/Experimental Study; Female; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - mortality; Humans; Hypoxia; Immune Checkpoint Inhibitors - therapeutic use; Male; Middle Aged; Prognosis; Protein Interaction Maps - genetics; Risk Assessment - methods; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - mortality; Transcriptome; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology
• ISSN: 0025-7974; 1536-5964; 1536-5964
• DOI: 10.1097/MD.0000000000039184

Increasing evidence has shown that hypoxia is a biomarker of tumor proliferation and metastasis. This research aimed to identify a hypoxia-associated gene prognostic index (HAGPI) in head and neck squamous cell carcinoma (HNSCC) and based on HAGPI-defined subgroups to predict prognosis and response to immune checkpoint inhibitors therapy. RNA-sequencing transcriptomic data for patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA). Protein-protein interaction network analysis was performed to select hypoxia-related hub genes. Univariate and multivariate cox regression analyses were used to identify hub genes to develop the HAGPI. Afterward expression data were imported into CIBERSORT to evaluate the relative proportion of 22 immune cells and compared the relative proportions of immune cells between the 2 HAGPI subgroups. The relationship between immunopheno score (IPS) and HAGPI was validated for immune checkpoint inhibitors (ICIs) response in TCGA cohorts. The HAGPI was constructed based on HS3ST1, HK1, PGK1, STC2, SERPINE1, PKLR genes. In high-HAGPI patients, the primary and secondary endpoint events in TCGA and GEO cohorts were significantly lower than low-HAGPI groups (P