E2F expression profiling-based subtypes in head and neck squamous cell carcinoma: clinical relevance, prognostic...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous malignancy with a poor prognosis.
• Dysregulation of E2F transcription factors (E2Fs), crucial regulators of cell proliferation and apoptosis, is implicated in HNSCC pathogenesis.

Purpose of the Study:

• To explore the molecular heterogeneity of HNSCC through E2F expression.
• To identify distinct HNSCC subtypes based on E2F expression.
• To develop a prognostic model integrating gene expression, immune infiltration, and drug sensitivity for HNSCC.

Main Methods:

• Analysis of the TCGA-HNSC dataset (n=494) using ConsensusClusterPlus to classify samples based on eight E2F expressions.
• Identification of differentially expressed genes and functional enrichment analysis using Gene Ontology and KEGG pathways.
• Construction and validation of a seven-gene prognostic model using LASSO regression and independent datasets, alongside estimation of immune cell infiltration and drug sensitivity.

Main Results:

• Two distinct E2F-based subtypes were identified: Cluster 1 (lower E2Fs) with poorer survival and enrichment in epidermal development and IL-17 signaling pathways, and Cluster 2 (higher E2Fs) with better survival and enrichment in DNA replication/repair pathways.
• High-risk patients showed increased M0 and M2 macrophage infiltration, indicating an immunosuppressive tumor microenvironment.
• The seven-gene prognostic model demonstrated robust performance (AUCs 0.673-0.692, C-index 0.66) and identified increased sensitivity to pazopanib and imatinib in high-risk patients.

Conclusions:

• Distinct E2F-based molecular subtypes of HNSCC exist, differing in prognosis, functional pathways, immune infiltration, and drug sensitivity.
• The developed prognostic model provides valuable risk stratification for HNSCC patients.
• The findings highlight potential biomarkers and therapeutic targets for HNSCC, warranting further validation.