Tumor-Specific Pro-Thrombotic Gene Expression in Head and Neck Squamous Cell Carcinoma: A Multi-Cohort Transcriptomic...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Venous thromboembolism (VTE) poses a variable risk in head and neck tumors.
• Understanding the molecular basis of VTE risk in head and neck squamous cell carcinoma (HNSCC) is crucial.
• Gene expression differences in coagulation pathways may underlie VTE risk variations.

Purpose of the Study:

• To compare coagulation-related gene expression in HNSCC versus esophageal (ESCCa) and lung (LUSC) squamous cell tumors.
• To investigate the relationship between clinicopathologic features of HNSCC and its coagulome gene expression profile.
• To identify potential drivers of tumor-specific pro-thrombotic potential in HNSCC.

Main Methods:

• Utilized RNA-sequencing data from The Cancer Genome Atlas (TCGA) for HNSCCa, ESCCa, and LUSC.
• Analyzed expression of pro-thrombotic genes (F3, SERPINE1, SERPINB2) and calculated a composite coagulome score.
• Correlated HNSCC coagulome expression with HPV status, tumor site, stage, grade, and demographics.

Main Results:

• HNSCCa exhibited significantly higher composite coagulome activation compared to LUSC and ESCCa (p < 0.001).
• HPV-negative HNSCC tumors showed higher coagulome expression than HPV-positive tumors (p < 0.001).
• Oral cavity tumors had the highest expression, oropharyngeal tumors the lowest; higher grade correlated inversely with expression.

Conclusions:

• HNSCCa displays a distinct pro-thrombotic gene expression profile, with significant heterogeneity influenced by HPV status and primary tumor location.
• The observed gene expression patterns suggest a tumor-specific pro-thrombotic potential rather than direct clinical VTE risk.
• Clinical manifestation of VTE in HNSCC likely requires additional factors such as inflammation or treatment interactions.