Sex-specific gene expression patterns in head and neck squamous cell carcinomas

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Head and neck squamous cell carcinomas (HNSCCs) disproportionately affect males, yet the underlying biological reasons remain unclear.
• Understanding sex-specific differences in HNSCC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate sex-specific gene expression patterns in HNSCC.
• To identify regulatory mechanisms contributing to observed sex differences.
• To explore the prognostic implications of sex-biased pathways.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) data, including RNA-seq, miRNA, and methylation profiles from 131 paired male and female HNSCC cases.
• Performed propensity score matching for case-control analysis.
• Analyzed differentially expressed genes (DEGs), pathway enrichment, immune cell infiltration, ceRNA networks, methylation, and differential coexpression.

Main Results:

• Males exhibited lower immune function activity and higher mitochondrial/ubiquitination activity compared to females.
• Pathway activities correlated with male prognosis, but not female prognosis.
• Identified eight sex-biased survival pathways, including five down-regulated immune pathways and three up-regulated pathways (GTP biosynthetic, DNA polymerase, spliceosomal).
• Found correlations between immune pathways and macrophage proportion.
• Discovered six over-expressed lncRNAs linked to up-regulated pathways, showing lower methylation in males.

Conclusions:

• Male HNSCC is characterized by immunosuppression, associated with unfavorable prognosis and macrophage infiltration.
• Sex-specific pathway alterations in HNSCC may be regulated by lncRNAs and methylation patterns.