# Coagulation factor II receptor-like 1 as a prognostic and immuno-modulatory factor in head and neck squamous cell carcinoma

## TL;DR

This study explores how a protein called F2RL1 is linked to worse outcomes and immune responses in head and neck cancer, suggesting it could help predict survival and guide treatment.

## Contribution

The study identifies F2RL1 as a reproducible biomarker for prognosis and immune modulation in HNSCC, supported by multi-cohort validation and multi-omics analysis.

## Key findings

- F2RL1 is significantly upregulated in HNSCC and associated with worse overall survival.
- F2RL1 correlates with immune cell infiltration, immune checkpoint genes, DNA methylation, and m6A regulators.
- A nomogram was developed to estimate 1-, 3-, and 5-year survival based on F2RL1 expression.

## Abstract

Head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer mortality, and robust biomarkers are needed for prognosis stratification and immuno-oncology research. We investigated coagulation factor II receptor-like 1 (F2RL1) in HNSCC, focusing on expression, clinical outcomes and immune associations.

RNA sequencing and clinical follow-up data from The Cancer Genome Atlas head and neck squamous cell carcinoma cohort (TCGA-HNSC) were analysed. Three independent Gene Expression Omnibus (GEO) cohorts (GSE9844, GSE55547 and GSE55548) were used for external confirmation, with preprocessing and differential-expression exports generated using Xiantao Academic. Immune infiltration, functional enrichment and multi-omics annotations were assessed. Experimental validation was performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry (IHC).

F2RL1 was significantly upregulated in HNSCC and was associated with worse overall survival (OS). Expression differences were consistent across the three GEO cohorts. F2RL1 showed significant associations with immune cell infiltration and immune checkpoint genes, and correlated with DNA methylation features and N6-methyladenosine (m6A) regulators. A nomogram was constructed to estimate 1-, 3- and 5-year OS.

F2RL1 is reproducibly overexpressed in HNSCC and is linked to adverse outcomes and immune-related features, supporting its potential as a prognostic biomarker and candidate therapeutic target.