标题：脑胶质瘤组织中FOXC1 mRNA的表达水平及其与预后的相关性

      作者：张跃欣 1，苏博 2，赵墨 1，魏康康 1，周国平 1    张跃欣 1，苏博 2，赵墨 1，魏康康 1，周国平 1南阳市中心医院神经外科 1、病理科 2，河南 南阳 473000

      卷次： 2023年34卷20期

      【摘要】 目的 探讨脑胶质瘤组织中叉头框C1 (FOXC1) mRNA表达水平及其与预后的相关性。方法 基于TCGA数据库中下载脑胶质瘤的基因表达谱数据和患者的临床-病理资料，比较701例脑胶质瘤组织及50例正常脑组织中FOXC1 mRNA表达水平的差异，多因素COX回归分析胶质瘤患者预后的危险因素，采用K-M曲线分析胶质瘤组织中FOXC1表达和总体生存率的关系，利用TIMER数据库分析胶质瘤组织中FOXC1表达与免疫细胞浸润程度的相关性。纳入我科20例脑胶质瘤患者和20例脑外伤患者作为研究对象，采用免疫组化法探讨胶质瘤组织及正常脑组织中FOXC1阳性表达率的差异。结果 脑胶质瘤组织和正常脑组织中FOXC1 mRNA表达水平分别为1.87 (1.54，2.16)和1.61 (1.14，1.92)，与正常脑组织比较，脑胶质瘤组织中FOXC1 mRNA表达水平显著升高，差异有显著统计学意义(P<0.01)。脑胶质瘤中FOXC1高表达和低表达患者的中位生存时间分别为933 d和2 835 d，脑胶质瘤中 FOXC1高表达生存率显著降低(HR=1.76，95%CI: 1.25~2.49，P=0.001)。经多因素COX回归分析证实，年龄(>40周岁)、WHO分级(G3)、IDH状态(突变型)、1p/19q 共缺失(非共缺失)和FOXC1 表达(高表达)是胶质瘤患者预后的独立影响因素。脑胶质瘤组织中FOXC1 mRNA表达和中性粒细胞(r=0.433，P<0.01)、巨噬细胞(r=0.400，P<0.01)、嗜酸性细胞(r=0.365，P<0.01)等细胞浸润程度呈显著正相关，与Tgd细胞(r=-0.115，P<0.05)、TFH细胞(r=-0.158，P<0.01)及 pDC细胞(r=-0.207，P<0.01)浸润程度呈显著负相关。免疫组化证实，20例胶质瘤组织中FOXC1高度阳性表达 14例，中度阳性表达 6例，正常的脑组织中 FOXC1无表达，差异具有显著统计学意义(P<0.01)。结论 FOXC1在脑胶质瘤组织中显著高表达，且FOXC1高表达与患者的不良预后相关，FOXC1可作为脑胶质瘤治疗的一个靶向标志物。
      【关键词】 胶质瘤；叉头框C1；预后；免疫细胞；相关性
      【中图分类号】 R739.41 【文献标识码】 A 【文章编号】 1003—6350（2023）20—2991—05

Expression level of FOXC1 mRNA in glioma and its correlation with prognosis.
ZHANG Yue-xin 1, SU Bo 2, ZHAOMo 1, WEI Kang-kang 1, ZHOU Guo-ping 1. Department of Neurosurgery 1, Department of Pathology 2, Nanyang CentralHospital, Nanyang 473000, Henan, CHINA
【Abstract】 Objective To investigate the expression level of FOXC1 mRNA in glioma tissue and its correlationwith prognosis. Methods The gene expression profile and clinico-pathological data of glioma from the TCGA databasewere downloaded. The differences of FOXC1 mRNA expression in glioma tissue (701 cases) and normal brain tissue(50 cases) were compared, and the prognostic risk factors of glioma patients were analyzed by multivariate COX regres-sion. K-M curve was used to analyze the relationship between FOXC1 expression and overall survival rate in glioma.The TIMER database was used to analyze the correlation between FOXC1 expression and the degree of immune cell in-filtration in glioma tissues. Twenty patients with glioma and twenty patients with traumatic brain injury in Department ofNeurosurgery were included. Immunohistochemical method was used to investigate the difference of FOXC1 positive ex-pression rate between glioma and normal brain tissue. Results FOXC1 mRNA expression levels in glioma tissue andnormal brain tissue were 1.87 (1.54, 2.16) and 1.61 (1.14, 1.92), respectively. Compared with normal brain tissues,FOXC1 mRNA expression levels in glioma tissues were significantly increased (P<0.01). The median survival time ofpatients with high and low FOXC1 expression in glioma was 933 d and 2 835 d, respectively, and the survival rate of pa-tients with high FOXC1 expression in glioma was significantly reduced (HR=1.76, 95%CI: 1.25-2.49, P=0.01). Multi-variate COX regression analysis confirmed that age (>40 years), WHO grade (G3), IDH status (mutant), 1p/19q codele-tion (non-codeletion), and FOXC1 expression (high expression) were independent prognostic factors of glioma. FOXC1mRNA expression in glioma tissue was positively correlated with the infiltration degree of neutrophils (r=0.433, P<0.01), macrophages (r=0.400, P<0.01), eosinophils (r=0.365, P<0.01). The Tgd cells (r=-0.115, P<0.05), TFH cells(r=-0.158, P<0.01), and pDC cells (r=-0.207, P<0.01) showed a significant negative correlation with FOXC1 mRNA ex-pression levels in glioma tissue. Immunohistochemistry confirmed that FOXC1 was highly expressed in 14 cases, moder-ately positive in 6 cases, while not expressed in normal brain tissues. The difference of FOXC1 expression between thetwo groups was statistically significant (P<0.01). Conclusion FOXC1 is significantly over-expressed in glioma tissues,and the high expression of FOXC1 is associated with poor prognosis of patients. FOXC1 may be used as a new targetedmarker for glioma therapy.
      【Key words】 Glioma; FOXC1; Prognosis; Immune cells; Correlation