FOXP3在卵巢癌肿瘤微环境中表达与生存预后关系的生物信息分析  

Bioinformatic analysis on expression of FOXP3 in tumor microenvironment of ovarian cancer and its relationship with survival prognosis

作　　者：林蓉沁 潘秀颉 卞丽红 Lin Rongqin;Pan Xiuxie;Bian Lihong(Chinese PLA Medical School,Beijing 100039,China;Beijing Immune Ark Medical Technology Co.,Ltd.,Beijing 100141,China;Fifth Medical Center of Chinese People’s Liberation Army General Hospital,Beijing 100071,China)

机构地区：[1]解放军医学院,北京市100039 [2]北京免疫方舟医药科技有限公司,北京市100141 [3]中国人民解放军总医院第五医学中心,北京市100071

出　　处：《中国组织工程研究》2025年第29期6343-6350,共8页Chinese Journal of Tissue Engineering Research

基　　金：北京市自然科学基金项目(18JS010);项目负责人:卞丽红。

摘　　要：背景:上皮性卵巢癌的肿瘤微环境中免疫细胞的比例和功能状态直接影响患者的预后及治疗响应。研究表明,CD4^(+)T细胞支持抗肿瘤免疫,在特定条件下可发挥抗肿瘤作用;CD8^(+)T细胞的高浸润被视为积极的预后标志;FOXP3^(+)Tregs则在维持免疫耐受和调节免疫反应中起关键作用。目的:通过生物信息算法对416例上皮性卵巢癌患者的数据信息及21例上皮性卵巢癌患者的临床病理样本进行综合分析,探讨CD4^(+)T细胞、CD8^(+)T细胞、FOXP3^(+)T细胞在卵巢癌肿瘤微环境的表达与生存预后的关系。方法:①通过非负矩阵分解算法对来自美国国家癌症研究所癌症基因组图谱的卵巢癌子数据集的416例上皮性卵巢癌患者进行分组。运用估算RNA转录子相对子集识别细胞类型算法对高生存率组和低生存率组患者的免疫细胞浸润程度进行差异分析。②收集在解放军总医院手术治疗的21例上皮性卵巢癌患者的病理组织,通过多重荧光免疫组织化学检测病理组织中的CD4、CD8、FOXP3因子,并分析其与患者预后的关系。结果与结论:在高生存率组中,CD4^(+)T细胞、CD8^(+)T细胞及FOXP3^(+)调节性T细胞等多种免疫细胞浸润比例显著高于低生存率组(P<0.01)。多重荧光免疫组织化学实验结果显示,FOXP3的高表达与卵巢癌患者更好的预后显著相关(P<0.05)。说明FOXP3在肿瘤微环境中的表达与上皮性卵巢癌患者的生存率相关,提示FOXP3^(+)调节性T细胞在肿瘤微环境中的浸润程度可能与上皮性卵巢癌患者的预后相关。BACKGROUND:The immune cell composition and functional states within the tumor microenvironment of epithelial ovarian cancer directly influence patient prognosis and therapeutic response.Recent studies indicate that CD4^(+)T cells not only support anti-tumor immunity but can also exert direct anti-tumor effects under specific conditions.High infiltration of CD8^(+)T cells is considered a positive prognostic marker.FOXP3^(+)regulatory T cells play a crucial role in maintaining immune tolerance and modulating immune responses.OBJECTIVE:The data from 416 epithelial ovarian cancer patients along with clinical pathology samples from 21 patients were comprehensively analyzed utilizing bioinformatics algorithms to investigate the relationship between the expression of CD4^(+)T cells,CD8^(+)T cells,and FOXP3^(+)T cells in the tumor microenvironment and survival outcomes in ovarian cancer patients.METHODS:(1)The study categorized 416 cases of epithelial ovarian cancer from the Ovarian Cancer subset of The Cancer Genome Atlas using the Non-negative Matrix Factorization algorithm.The CIBERSORT algorithm(Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts)was employed to examine differences in immune cell infiltration between patients with high and low survival rates.(2)Multiplex immunohistochemistry was used to assess the expression of CD4,CD8,and FOXP3 in pathological tissue samples from 21 patients from Chinese People’s Liberation Army General Hospital,and their association with patient prognosis was analyzed.RESULTS AND CONCLUSION:The high survival rate group exhibited significantly greater infiltration of immune cells,including CD4^(+)T cells,CD8^(+)T cells,and FOXP3^(+)regulatory T cells,compared with the low survival rate group(P<0.01).Results from the multiplex immunohistochemistry experiments revealed that high expression of FOXP3 was significantly correlated with better prognosis in ovarian cancer patients(P<0.05).It is indicated that the expression of FOXP3 in the tumor microenvironment is

关 键 词：上皮性卵巢癌 FOXP3 非负矩阵分解 肿瘤微环境 疾病预后 工程化细胞因子 

分 类 号：R496[医药卫生—康复医学] R318[医药卫生—临床医学] R730.3