ANXA5 predicts prognosis and immune response and mediates proliferation and migration in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that often develops unnoticed. Typically, these tumors are identified at advanced stages, resulting in a relatively low chance of successful treatment. Anoikis serves as a natural defense against the spread of tumor cells, meaning circumventing anoikis can effectively inhibit tumor metastasis. Nonetheless, studies focusing on anoikis in the context of HNSCC remain scarce.

Methods: Anoikis-related genes (ARGs) were identified by using the GeneCards and Harmonizome databases. Expression data of these genes and relevant clinical features were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A LASSO regression and a prognostic risk score model were developed to determine their prognostic significance. The analysis included the use of the CIBERSORT algorithm to quantify immune and stromal cell presence. Furthermore, in vitro and in vivo, we confirmed the expression and functional roles of proteins and mRNA of genes independently predictive of prognosis.

Results: The study identified eight genes linked to prognosis (ANXA5, BAK1, CDKN2A, PPARG, CCR7, MAPK11, CRYAB, CRYBA1) and developed a prognostic model that effectively forecasts the survival outcomes for patients with HNSCC. A higher survival likelihood is associated with lower risk scores. In addition, a significant relationship was found between immune and risk score, and ANXA5 deletion promoted the killing of HNSCC cells by activated CD8 T cells. During the screening process, 65 different chemotherapeutic drugs were found to have significant differences in IC50 values when comparing high- and low-risk categories. ANXA5 emerged as a gene with independent prognostic significance, exhibiting notably elevated protein and mRNA levels in HNSCC tissue compared to non-tumorous tissue. The suppression of ANXA5 gene activity resulted in a substantial decrease in both the growth and mobility of HNSCC cells. Animal model experiments demonstrated that inhibiting ANXA5 suppressed HNSCC growth and migration in vivo.

Conclusion: Through bioinformatics, a prognostic risk model of high precision was developed, offering valuable insights into the survival rates and immune responses in patients with HNSCC. ANXA5 is highlighted as a significant prognostic factor among the identified genes, indicating its promise as a potential therapeutic target for those with HNSCC.