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Exploring TROP2 expression in oropharyngeal squamous cell carcinoma: Association with prognosis and tumor immune
Juliana Mota Siqueira1, Daniele Heguedusch1, Mateus Trinconi Cunha2
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA; Department of Stomatology, Discipline of Oral and Maxillofacial Pathology, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil.
Abstract:
Oropharyngeal squamous cell carcinoma (OPSCC) presents prognostic and therapeutic challenges. Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein involved in oncogenic signaling pathways and has been explored as a therapeutic target in many solid tumors. This study aims to evaluate the prevalence and prognostic significance of TROP2 expression in OPSCC and explore its association with the tumor immune microenvironment composition. A cohort of 112 OPSCC patients from two high-volume cancer centers was retrospectively analyzed. TROP2 expression was assessed by immunohistochemistry and categorized into negative/low versus moderate/high. Transcriptomic analysis was performed in a subset of samples to explore immune microenvironment correlations. Survival analyses were conducted using Kaplan-Meier curves and Cox regression models. Moderate/high TROP2 expression was observed in 42 % of patients and was significantly associated with lower levels of smoking and alcohol exposure, reduced rates of perineural invasion, and fewer positive lymph nodes. Patients with moderate/high TROP2 expression demonstrated a trend toward improved overall survival (OS) (HR = 0.54, P = 0.07) and significantly prolonged disease-free survival (DFS) (HR = 0.46, P = 0.03). In TCGA validation Kaplan-Meier survival analysis demonstrated that patients with high TROP2 gene expression had significantly improved OS compared to those with low TROP2 expression (P = 0.012, HR = 0.361 [0.14-0.93]). Transcriptomic analysis revealed an enrichment of cytotoxic immune populations in tumors with high TROP2 expression. In OPSCC patients, high TROP2 expression was associated with more favorable pathologic characteristics, improved DFS, and a higher presence of cytotoxic immune cells in the tumor microenvironment.
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