BAG3 Positivity as Prognostic Marker in Head and Neck Squamous Cell Carcinoma

Background: Head and neck squamous cell carcinoma (HNSCC) exhibit considerable heterogeneity, complicating the prediction of disease progression and treatment response. Consequently, researchers are actively investigating reliable biomarkers to forecast disease trajectories and inform therapeutic decisions. This study examines the role of BAG3, a protein involved in cell survival and stress response, as a potential predictive marker in HNSCC. The objective is to analyze BAG3 expression across various HNSCC types and correlate it with disease-free survival (DFS), aiming to elucidate the influence of BAG3 positivity on cancer progression. Methods: A multi-institutional retrospective study was conducted by analyzing BAG3 expression by immunohistochemistry in 104 tissue samples from patients with head and neck squamous cell carcinoma (HNSCC). The data were then correlated with DFS to assess the impact of BAG3 positivity on prognosis. Results: Immunohistochemical analysis of primary tumor samples collected from therapy-naive patients showed that BAG3 positivity was widespread across different head and neck cancer sites, with no significant correlation to sex, smoking status, HPV infection, tumor location, grade, or TNM parameters. However, BAG3 high positive patients had shorter DFS (median 23.2 months) compared to BAG3-negative patients (median 31.3 months). Cox analysis revealed that BAG3 high expression by IHC was associated with a more than 3-fold increased risk of disease recurrence. Conclusions: This study is the first to explore BAG3 as a biomarker for HNSCC recurrence. While preliminary findings suggest a link between BAG3 positivity and increased recurrence risk, further research is needed to validate these results. Prospective studies could help establish BAG3's prognostic value and potentially lead to more personalized treatment approaches for HNSCC.