NF-Y Subunits Overexpression in HNSCC.

Area of Science:

• Molecular Biology
• Cancer Genomics
• Epigenetics

Background:

• NF-Y is a CCAAT-binding transcription factor complex crucial for gene regulation.
• The CCAAT box is frequently found in promoters of genes implicated in cancer.
• Previous studies indicated NF-YA overexpression in various cancers like breast, lung, and liver.

Purpose of the Study:

• To investigate the role and expression patterns of NF-Y subunits in head and neck squamous cell carcinomas (HNSCC).
• To analyze the correlation between NF-Y expression, tumor subtypes, and patient survival.
• To explore the association of NF-Y with specific cellular populations and tumor characteristics.

Main Methods:

• Analysis of The Cancer Genome Atlas (TCGA) RNA-seq datasets for HNSCC.
• Subtyping of TCGA data and deconvolution of single-cell RNA-seq (scRNA-seq) data.
• Derivation of survival curves and correlation analyses.

Main Results:

• CCAAT box enrichment was observed in promoters of overexpressed genes in HNSCC.
• Short NF-YA (NF-YAs) was overexpressed across all HNSCC subtypes, while long NF-YAl was elevated in the Mesenchymal subtype.
• NF-YAl expression correlated with p53 mutations and was associated with Cancer Associated Fibroblasts (CAFs) and prometastatic p-EMT cells.
• In HPV-positive tumors, high NF-YAs, p16, and ΔNp63 expression correlated with better prognosis.

Conclusions:

• Overexpression of histone fold domain (HFD) subunits and NF-YAs appears protective in HPV-positive HNSCC.
• NF-YAl expression is predominantly found in p53-mutated tumors and malignant p-EMT cells, suggesting a role in aggressive cancer phenotypes.
• NF-Y subunits exhibit differential expression and prognostic significance in HNSCC, highlighting their complex role in cancer.