调节性T细胞与卵巢癌的病理进程、肿瘤负荷、预后结局相关性调查研究

    Study on the correlation between regulatory T cells and pathological process, tumor burden and prognosis of ovarian cancer

    • 摘要:
      目的: 探讨卵巢癌病人外周血中调节性T细胞与病理进程、肿瘤负荷及病人预后结局的关系。
      方法: 选取张家口市第一医院妇产科确诊且符合纳入条件的卵巢癌病人64例(卵巢癌组)、另外选择同期确诊的卵巢良性肿瘤病人80例作为良性组,采用流式细胞仪技术检测2组病人外周血中CD4+CD25+Foxp3+/CD4+、CD8+CD28-/CD8+及CD8+Foxp3+/CD8+细胞表达水平,并按照不同的病理学特征、外周血循环肿瘤细胞(CTC)检出结果进行分层对比分析,采用logistic回归模型分析调节性T细胞与病人3年随访结局的关系。
      结果: 卵巢癌组病人的外周血中CD4+CD25+Foxp3+/CD4+、CD8+CD28-/CD8+及CD8+Foxp3+/CD8+细胞表达水平均高于良性组(P < 0.05);FIGO分期(Ⅲ+Ⅳ期)、低分化、发生淋巴结转移、CTC阳性的卵巢癌病人的外周血中CD4+CD25+Foxp3+/CD4+细胞表达水平均高于FIGO分期(Ⅰ+Ⅱ期)、高+中分化、未发生淋巴结转移、CTC阴性的卵巢癌病人(P < 0.05);FIGO分期(Ⅲ+Ⅳ期)、低分化、发生淋巴结转移的卵巢癌病人的外周血中CD8+CD28-/CD8+细胞表达水平均明显高于FIGO分期(Ⅰ+Ⅱ期)、高+中分化、未发生淋巴结转移的卵巢癌病人(P < 0.01);FIGO分期(Ⅲ+Ⅳ期)、低分化的卵巢癌病人的外周血中CD8+Foxp3+/CD8+细胞表达水平均明显高于FIGO分期(Ⅰ+Ⅱ期)、高+中分化的卵巢癌病人(P < 0.01)。logistic回归模型结果显示:外周血CD4+CD25+Foxp3+/CD4+表达增高、CD8+CD28-/CD8+表达增高、CD8+Foxp3+/CD8+表达增高、FIGO分期(Ⅲ+Ⅳ期)、低分化、CTC阳性是卵巢癌病人不良预后的独立危险因素(P < 0.05 ~ P < 0.01)。
      结论: 外周血中调节性T细胞与卵巢癌的FIGO分期、肿瘤分化程度等肿瘤进展程度指标有关,CD4+CD25+Foxp3+/CD4+表达与病人外周血CTC阳性表达有关,外周血中调节性T细胞高表达是卵巢癌病人不良预后结局的独立危险因素。

       

      Abstract:
      Objective To investigate the relationship between regulatory T cells in peripheral blood and pathological process, tumor burden and prognosis of patients with ovarian cancer.
      Methods Sixty-four patients with ovarian cancer in the obstetrics and Gynecology department of Zhangjiakou First Hospital were selected (ovarian cancer group), and 80 patients with benign ovarian tumor at the same time were selected as benign group. Flow cytometry was used to detect the expression levels of CD4+CD25+Foxp3+/CD4+, CD8+CD28-/CD8+ and CD8+Foxp3+/CD8+ cells in two groups. Two groups were stratified and compared according to different pathological characteristics and detection results of circulating tumor cells (CTC) in peripheral blood. Logistic regression model was used to analyze the relationship between regulatory T cells and 3-year follow-up outcomes.
      Results The expression levels of CD4+CD25+Foxp3+/CD4+, CD8+CD28-/CD8+ and CD8+Foxp3+/CD8+ cells in the peripheral blood of ovarian cancer group were significantly higher than those of benign group (P < 0.05). The expression level of CD4+CD25+Foxp3+/CD4+cells in peripheral blood of ovarian cancer patients with FIGO stage (Ⅲ+Ⅳ), low differentiation, lymph node metastasis and CTC-positive was significantly higher than that of ovarian cancer patients with FIGO stage (Ⅰ+Ⅱ), high and medium differentiation, non-lymph node metastasis and CTC-negative (P < 0.05). The expression level of CD8+CD28-/CD8+ cells in peripheral blood of ovarian cancer patients with FIGO stage (Ⅲ+Ⅳ), low differentiation and lymph node metastasis were significantly higher than that of ovarian cancer patients with FIGO stage (Ⅰ+Ⅱ), high and medium differentiation and non-lymph node metastasis (P < 0.05). The expression level of CD8+Foxp3+/CD8+ cells in peripheral blood of ovarian cancer patients with FIGO stage (Ⅲ+Ⅳ) and low differentiation was significantly higher than that of ovarian cancer patients with FIGO stage (Ⅰ+Ⅱ) and high and medium differentiation (P < 0.05). The results of Logistic regression model showed the expression levels of CD4+CD25+Foxp3+/CD4+, CD8+CD28-/CD8+ and CD8+Foxp3+/CD8+ increasing, FIGO stage (Ⅲ+Ⅳ), low differentiation and positive CTC were the independent risk factors of poor prognosis of ovarian cancer patients (P < 0.05).
      Conclusions The regulatory T cells in peripheral blood is related to the FIGO stage of ovarian cancer, degree of tumor differentiation and other tumor progression indicators. The expression of CD4+CD25+Foxp3+/CD4+ is related to the positive expression of CTC in patients' peripheral blood. The high expression of regulatory T cells in peripheral blood is an independent risk factor for poor prognostic outcome in patients with ovarian cancer.

       

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