Integrating single-cell RNA-seq and bulk RNA-seq to construct a neutrophil prognostic model for predicting prognosis and immune response in oral squamous cell carcinoma

Hum Genomics. 2024 Dec 26;18(1):140. doi: 10.1186/s40246-024-00712-7.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with poor prognosis. Neutrophil infiltration has been associated with unfavorable outcomes in OSCC, but the underlying molecular mechanisms remain unclear.

Methods: This study integrated single-cell transcriptomics (scRNA-seq) with bulk RNA-seq data to analyze neutrophil infiltration patterns in OSCC and identify key gene modules using weighted gene co-expression network analysis (hdWGCNA). A prognostic model was developed based on univariate and Lasso-Cox regression analyses, stratifying patients into high- and low-risk groups. Immune landscape and drug sensitivity analyses were conducted to explore group-specific differences. Additionally, Mendelian randomization analysis was employed to identify genes causally related to OSCC progression.

Results: Several key pathways associated with neutrophil interactions in OSCC progression were identified, leading to the construction of a prognostic model based on significant module genes. The model demonstrated strong predictive performance in distinguishing survival rates between high- and low-risk groups. Immune landscape analysis revealed significant differences in cell infiltration patterns and TIDE scores between the groups. Drug sensitivity analysis highlighted differences in drug responsiveness between high- and low-risk groups.

Conclusion: This study elucidates the critical role of neutrophils and their associated gene modules in OSCC progression. The prognostic model provides a novel reference for patient stratification and targeted therapy. These findings offer potential new targets for OSCC diagnosis, prognosis, and immunotherapy.

Keywords: Biomarkers; Immune landscape; Neutrophils; Oral squamous cell carcinoma; Risk model.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks
  • Humans
  • Male
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / immunology
  • Mouth Neoplasms* / pathology
  • Neutrophil Infiltration / genetics
  • Neutrophils* / immunology
  • Neutrophils* / pathology
  • Prognosis
  • RNA-Seq*
  • Single-Cell Analysis* / methods
  • Single-Cell Gene Expression Analysis
  • Transcriptome / genetics
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor