# Characterization of ANXA1 in chemotherapy resistance of head and neck squamous cell carcinoma: insights from artificial intelligence and integrative bioinformatics analysis

## TL;DR

This study identifies ANXA1 as a key biomarker linked to chemotherapy resistance in head and neck cancer, offering potential for personalized treatment strategies.

## Contribution

The study introduces ANXA1 as a novel, druggable biomarker for HNSCC and proposes BRD-K10482608 as a potential therapeutic agent.

## Key findings

- ANXA1 is downregulated and associated with HNSCC progression and poor prognosis.
- BRD-K10482608 shows potential as a therapeutic agent for targeting ANXA1 in HNSCC.
- AI and bioinformatics tools identified ANXA1 as a key player in chemotherapy resistance.

## Abstract

Head and neck squamous cell carcinoma (HNSCC) exhibits intensive chemoresistance (CR), leading to frequent recurrence and poor prognosis; however, actionable biomarkers and therapeutic options remain limited.

By utilizing bulk profiles of HNSCC patients (TCGA-HNSCC cohort and GSE6631) from TCGA and GEO databases, we identified CR-associated DEGs via Limma and WGCNA frameworks. Importantly, LASSO–Cox regression was utilized for the construction of a predictive model and identification of the CR-associated hub gene in TCGA-HNSCC cohort. In addition, predictive model performance was validated in the HNSCC patient bulk profile (GSE65858). Furthermore, the molecular and immune characteristics of the hub gene were estimated at HNSCC patient bulk (TCGA-HNSCC cohort) and single-cell (GSE163872) levels, especially in artificial intelligence (AI)-empowered virtual cells. Specifically, AI-driven therapeutic framework (RefLector) and molecular docking were performed for the recognition of an optimal therapeutic framework for the treatment of HNSCC by targeting the hub gene. Finally, the cariogenic role of the hub gene was evaluated in an in vitro study.

CR-associated DEGs can guide the risk stratification of HNSCC patients. ANXA1 was identified as a downregulated, malignancy-distributed, prognostic, and druggable biomarker for HNSCC patients, which was also associated with HNSCC progression. BRD-K10482608 can be considered a potential therapeutic agent for the treatment of HNSCC.

Our study highlighted the CR in risk stratification for HNSCC patients and ANXA1 in the pathogenesis of HNSCC, which can guide personalized and precision medicine for HNSCC patients.