High Tumoral CD24 Expression and Low CD3⁺ Tumor-Infiltrating Lymphocytes as a Biomarker for High-Risk Locally...

Introduction: The limited value of TNM staging in locally advanced (LA) nasopharyngeal carcinoma (NPC), defined as stage III or IV NPC, highlights the need for prognostic markers. Here, we aimed to evaluate the ability of the cancer stem cell markers, BMI1, ALDH1, CD44, and CD24, and the epithelial-mesenchymal transition marker, vimentin, as novel prognostic markers in LA-NPC. Methods: A cohort of 83 patients with LA-NPC, previously recruited for another trial with a different goal, was used. The marker expression in tissue sections was evaluated using immunohistochemistry, and the association of expression with survival outcomes was analyzed using the Kaplan-Meier method and Cox regression analysis. Results: The expression of BMI1 and ALDH1 was not associated with survival. The tumoral expression of CD24, CD44, and vimentin was significantly associated with disease-free survival (DFS), whereas only the expression of CD24 was also significantly associated with overall survival (OS). Indeed, CD24 expression emerged as an independent prognostic factor as it was associated with survival in univariate and multivariate Cox regression analysis. Interestingly, combining the status of CD24 expression in tumor cells with the density of CD3⁺ tumor-infiltrating lymphocytes (TIL), a microenvironment/immune-related marker, identified a high-risk subgroup with the worst DFS and OS. Conclusions: These results suggest the utility of combining tumoral CD24 expression and the CD3⁺ TIL density as a prognostic factor in LA-NPC, with potential application in disease management and future trial design. Our findings also highlight the potential of combining immune- and cancer stem cell-related factors in personalized treatment strategies for cancer.