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[摘要]
[摘 要] 目的:探究CD24在睾丸生殖细胞瘤中的表达、功能及临床意义。方法:本研究共纳入204例睾丸生殖细胞瘤患者,其 中包括TCGA数据库和长海医院睾丸生殖细胞瘤队列(TGCT-Changhai队列)。通过预后分析和多变量分析评估CD24表达与临床 特征的关联性,并运用肿瘤组织免疫组化(IHC)染色技术解析CD24调控TGCT肿瘤免疫微环境(TIME)的作用机制。最终通过分 析CD24高表达组与低表达组中PD-L1表达水平和肿瘤相关巨噬细胞(TAM)M2型浸润的差异,并运用TIDE算法进一步探讨了CD24 表达水平与免疫逃逸评分和免疫治疗响应率间的关系。结果:TCGA数据库分析显示,CD24在高临床分期和高M分期睾丸生殖 细胞瘤中的表达呈现显著上调趋势(P < 0.05);与瘤旁组织相比,CD24在睾丸生殖细胞瘤和转移瘤组织中的表达显著上调(P < 0.05); 在不同TNM分期和肿瘤进展情况的睾丸生殖细胞瘤中,CD24的表达水平差异均有统计学意义(均P < 0.05);单因素Logistic回归 分析表明,CD24可以作为睾丸生殖细胞瘤患者临床结局的预测因子[OR = 0.135,95% CI (0.035,0.516),P = 0.003],多因素分析进 一步确认其作为独立预测因子的地位[OR = 0.057,95% CI (0.005,0.624),P = 0.019];睾丸生殖细胞瘤组织中CD24 mRNA表达水 平与免疫细胞标志物CD206和CD70表达水平均相关(均P < 0.05),并且CD24表达水平在免疫逃逸分数评分和免疫治疗响应率评 估中具有重要预测意义。结论:睾丸生殖细胞瘤组织中CD24呈高表达,且CD24表达与睾丸生殖细胞瘤患者的预后显著相关,是 睾丸生殖细胞瘤生物治疗的潜在新靶点。
[Key word]
[Abstract]
[Abstract] Objective: To investigate the expression, function, and clinical significance of CD24 in testicular germ cell tumors (TGCT). Methods: This study included 204 testicular germ cell tumor (TGCT) patients from the TCGA database and the TGCT-Changhai testicular germ cell tumor cohort (Changhai Hospital cohort). Prognostic analysis and multivariate analysis were employed to evaluate the association between CD24 expression and clinical characteristics. Immunohistochemistry (IHC) staining of tumor tissues was used to elucidate the mechanism by which CD24 regulated the tumor immune microenvironment (TIME) in TGCT. Finally, by analyzing the diffrences in PD-L1 expression levels and tumor-associated macrophage (TAM) M2-type cell infiltration rates between CD24 high-expression and low-expression groups, and employing the TIDE algorithm, we investigated the correlation between CD24 expression levels and immune escape scores as well as immunotherapy response rates. Results: Analysis of the TCGA database revealed that CD24 expression was significantly upregulated in TGCT with high clinical staging and M-stage (P < 0.05). Compared to adjacent normal tissues, CD24 expression was significantly elevated in both primary and metastatic TGCT tissues (P < 0.05). Significant differences in CD24 expression levels were observed across TNM stages and tumor progression statuses (all P < 0.05). Univariate logistic regression analysis identified CD24 as a predictive factor for clinical outcomes in TGCT patients (OR = 0.135, 95% CI [0.035, 0.516], P = 0.003), and multivariate analysis further confirmed its role as an independent predictor (OR = 0.057, 95% CI [0.005, 0.624], P = 0.019). In TGCT tissues, CD24 mRNA levels correlated with immune cell markers CD206 and CD70 (all P < 0.05). Additionally, CD24 expression levels demonstrated significant predictive value in immune escape scoring and immunotherapy response rate assessments. Conclusions: CD24 is highly expressed in TGCT tissues and its expression is significantly correlated with the prognosis of TGCT patients, which makes it a potential new target point of biotherapy for testicular germ cell tumor patients.
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[基金项目]
上海申康医院发展中心临床科技创新项目(SHDC12021118);上海市自然科学基金(22ZR1477800)