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.
引言：局部晚期（LA）鼻咽癌（NPC）定义为III期或IV期鼻咽癌，其TNM分期的预测价值有限，这凸显了对预后标志物的需求。本研究旨在评估癌症干细胞标志物BMI1、ALDH1、CD44和CD24，以及上皮-间质转化标志物波形蛋白（vimentin）作为局部晚期鼻咽癌新型预后标志物的潜力。 方法：本研究纳入了83例局部晚期鼻咽癌患者队列，这些患者先前因另一项不同目的的研究而被招募。通过免疫组织化学方法评估组织切片中标志物的表达，并采用Kaplan-Meier法和Cox回归分析评估表达水平与生存结局之间的关联。 结果：BMI1和ALDH1的表达与生存无关。CD24、CD44和波形蛋白在肿瘤中的表达与无病生存期（DFS）显著相关，而仅CD24的表达也与总生存期（OS）显著相关。事实上，CD24表达在单变量和多变量Cox回归分析中均与生存相关，因此成为一个独立的预后因素。有趣的是，将肿瘤细胞中CD24的表达状态与CD3+肿瘤浸润淋巴细胞（TIL）密度（一种微环境/免疫相关标志物）相结合，识别出了一个具有最差DFS和OS的高风险亚组。 结论：这些结果表明，结合肿瘤CD24表达和CD3+TIL密度可作为局部晚期鼻咽癌的预后因素，在疾病管理和未来试验设计中具有潜在应用价值。我们的发现还强调了在癌症个体化治疗策略中结合免疫相关因素和癌症干细胞相关因素的潜力。
肿瘤(癌症)患者之家