Single-cell insights into HNSCC tumor heterogeneity and programmed cell death pathways

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Head and neck squamous cell carcinoma (HNSCC) presents significant mortality and recurrence risks, often diagnosed at advanced stages.
• Understanding HNSCC heterogeneity is crucial for improving therapeutic strategies and patient outcomes.

Purpose of the Study:

• To investigate HNSCC tumor subpopulations using single-cell RNA sequencing (scRNA-seq).
• To identify novel prognostic markers and therapeutic targets within HNSCC.
• To refine prognostic models for head and neck squamous cell carcinoma.

Main Methods:

• Pseudotime trajectory and stemness analyses were applied to HNSCC tumor subpopulations.
• Programmed death and metabolic pathways were examined in distinct subpopulations.
• A prognostic model was developed using LASSO regression and the MALAT1 Tumors Risk Score (MTRS).

Main Results:

• The C2 MALAT1+ Tumors subpopulation displayed reduced expression of programmed death and metabolic pathways.
• Key transcription factors (LEF1, RFX3, CREM, MZF1, ZNF202) and risk genes (ADM, RPL31, EIF5B, TAF7) were identified.
• A high MTRS correlated with worse survival, higher tumor purity, enriched CD4 memory T cells, and increased sensitivity to specific chemotherapies.

Conclusions:

• ScRNA-seq elucidated HNSCC heterogeneity, particularly the C2 MALAT1+ Tumors subpopulation.
• Novel prognostic markers and therapeutic targets were identified, advancing understanding of HNSCC progression and drug resistance.