Establishment of a prognostic model for hypoxia-associated genes in OPSCC and revelation of intercellular crosstalk

Yichen Zhao ¹, Jintao Yu ¹, Chang Zheng ¹

⁰Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Hospital of China Medical University, Shenyang, China.

Frontiers in Immunology +

|

June 18, 2024

View abstract on PubMed

Summary

This study identifies two distinct hypoxia subtypes in oropharyngeal squamous cell carcinoma (OPSCC), linking specific gene profiles to patient prognosis and immune response. Findings suggest HPV-positive tumors with low hypoxia exhibit better outcomes and treatment sensitivity.

Area Of Science

Oncology
Immunology
Genomics

Background

Hypoxia significantly impacts the tumor microenvironment, immune response, and treatment outcomes in oropharyngeal squamous cell carcinoma (OPSCC).
Understanding hypoxia's role is crucial for developing effective therapeutic strategies.

Purpose Of The Study

To identify and characterize hypoxia subtypes in OPSCC.
To investigate the relationship between hypoxia, immune infiltration, and patient prognosis.
To explore the potential of hypoxia-related genes as prognostic markers and predict immunotherapy response.

Main Methods

Consistency clustering and weighted gene correlation network analysis (WGCNA) on OPSCC bulk sequencing data.
CIBERSORT for immune infiltration, Gene Set Enrichment Analysis (GSEA) for functional enrichment.
Univariate Cox and LASSO regression for prognostic model construction.
scRNA-seq, TSNE clustering, scissors algorithm, and Cellchat for cellular analysis.
TIDE algorithm for immunotherapy response prediction.

Main Results

Two hypoxia subtypes were identified in OPSCC.
A prognostic model for seven hypoxia-related genes was constructed.
Low hypoxia and low-risk groups showed a prevalence of HPV-positive patients.
Low TDO2 expression was observed in HPV-positive (P16-positive) patients.
HPV16 E7's role in inhibiting HIF-1α, reducing glycolysis, and improving prognosis was predicted.
scRNA-seq and scissors algorithm effectively classified cell types based on hypoxia.
Significant cellular crosstalk among epithelial, fibroblast, and endothelial cells was identified.

Conclusions

Hypoxia subtypes in OPSCC are associated with distinct clinical characteristics and immune microenvironments.
Hypoxia-related genes can serve as prognostic markers and predict immunotherapy response.
HPV-positive OPSCC with low hypoxia demonstrates better prognosis and treatment sensitivity, potentially mediated by HPV16 E7's effect on glycolysis.
Cellular communication networks within the tumor microenvironment are influenced by hypoxia and contribute to tumor progression.

Keywords:

HIF-1α human papillomavirus hypoxia oropharyngeal squamous cell carcinomas single-cell

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