上皮性卵巢肿瘤患者外周血和腹水T淋巴细胞凋亡和Fas表达特点及其与CA125关系的研究

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目的了解卵巢肿瘤患者外周血和腹水 T 淋巴细胞凋亡和 Fas(CD95)表达特点及其与 CA125的关系。方法应用流式细胞术测定18例Ⅲ~Ⅳ期卵巢癌患者(Ⅲ~Ⅳ期组),15例Ⅰ~Ⅱ期卵巢癌患者(Ⅰ~Ⅱ期组),Ⅲ~Ⅳ期组患者手术加化疗后(治疗后组),18例良性上皮性卵巢肿瘤患者(良性组),6例库肯勃氏瘤患者(库肯勃氏瘤组)及20例正常体检女性(正常组)的外周血 T淋巴细胞凋亡和 Fas 表达,并测定上述治疗前的卵巢癌患者和库肯勃氏瘤患者的腹水 T 淋巴细胞以及良性组中10例患者(良性盆腔积液组)的盆腔积液 T 淋巴细胞的凋亡和 Fas 表达。同时测定卵巢癌患者外周血 CA125的水平。结果Ⅲ~Ⅳ期组患者的外周血 T 淋巴细胞凋亡阳性率为5.55(3.57~9.62)%,明显高于正常组、良性组、Ⅰ~Ⅱ期组(P<0.01)和治疗后组(P<0.05),Ⅲ~Ⅳ期组患者外周血 T 淋巴细胞的 Fas 表达强度为51±10,明显高于正常组(P<0.05)。Ⅰ~Ⅱ期组和Ⅲ~Ⅳ期组患者腹水 T 淋巴细胞的凋亡阳性率,T 淋巴细胞的 Fas 阳性率,Fas 表达强度分别为17.41(7.06~24.56)%,(57±16)%,(55±11)%和34.06(17.03~44.65)%,(66±12)%,(70±24)%,均高于良性盆腔积液组的0.78(0.67~1.4J4)%,(37±6)%,(43±6)%(P<0.01)。Ⅲ~Ⅳ期组的凋亡阳性率和 Fas 阳性率均明显高于库肯勃氏瘤组(P<0.01)。Ⅰ~Ⅱ期组患者腹水 T 淋巴细胞凋亡与血清 CA125水平呈正相关(r=0.77,P=0.009)。血清 CA125>500 KU/L 的卵巢癌患者腹水 T 淋巴细胞的凋亡高于 CA125≤500 KU/L 的患者(P=0.009)。结论 (1)T 淋巴细胞凋亡上调出现于较早期卵巢癌患者的腹腔局部和晚期患者的外周血,而且晚期卵巢癌腹水 T 淋巴细胞凋亡和Fas 表达高于库肯勃氏瘤患者,反映了原发卵巢癌腹腔局部免疫缺陷的特殊性。(2)有效的治疗可以降低卵巢癌患者外周血 T 淋巴细胞的凋亡。(3)卵巢癌腹水 T 淋巴细胞的 Fas 表达显著上调,是卵巢肿瘤免疫治疗的重要靶点。(4)CA125能间接反映卵巢癌腹腔局部的免疫状况。 Objective To investigate the characteristics of T lymphocyte apoptosis and expression of Fas (CD95) in peripheral blood and ascites of ovarian cancer patients and its relationship with CA125. Methods 18 patients with stage Ⅲ ~ Ⅳ ovarian cancer (Ⅲ ~ Ⅳ group) and 15 patients with stage Ⅰ ~ Ⅱ ovarian cancer (Ⅰ ~ Ⅱ group) were treated by flow cytometry. Patients in stage Ⅲ ~ Ⅳ were treated with chemotherapy (Post-treatment group), 18 patients with benign epithelial ovarian tumor (benign group), 6 patients with Kubinker’s tumor (Kokenburnoma group) and 20 normal women (normal group) Lymphocyte apoptosis and Fas expression, and the determination of ascites T lymphocytes in the above-mentioned pre-treatment ovarian cancer patients and in the patients with Kukumberg tumors as well as the pelvic fluid T lymphocytes in 10 patients (benign pelvic fluid group) in the benign group Apoptosis and Fas expression. At the same time, the level of CA125 in peripheral blood of patients with ovarian cancer was determined. Results The positive rate of T lymphocyte apoptosis in peripheral blood of patients in group Ⅲ ~ Ⅳ was 5.55 (3.57 ~ 9.62)%, which was significantly higher than that in normal group, benign group, Ⅰ ~ Ⅱ group (P <0.01) P <0.05). The expression of Fas in peripheral blood T lymphocytes in stage Ⅲ ~ Ⅳ group was 51 ± 10, which was significantly higher than that in normal group (P <0.05). The positive rate of T lymphocyte apoptosis, the positive rate of Fas in T lymphocytes and the expression of Fas in stage Ⅰ ~ Ⅱ and Ⅲ ~ Ⅳ groups were 17.41 (7.06 ~ 24.56)% and (57 ± 16)% respectively, Were significantly higher than those in benign pelvic effusion group (55 ± 11) and 34.06 (17.03 ± 44.65)%, (66 ± 12)% and (70 ± 24)%, respectively, 6)%, (43 ± 6)% (P <0.01). The positive rate of apoptosis and the positive rate of Fas in stage Ⅲ ~ Ⅳ were significantly higher than that in the group of Kubinker’s tumor (P <0.01). There was a positive correlation between apoptosis of ascites T lymphocytes and serum CA125 levels in stage Ⅰ ~ Ⅱ patients (r = 0.77, P = 0.009). Apoptosis of T lymphocytes in patients with ovarian cancer with serum CA125> 500 KU / L was higher than those with CA125 ≤ 500 KU / L (P = 0.009). Conclusions (1) T lymphocyte apoptosis is upregulated in the peripheral blood of patients with early and late stage ovarian cancer, and the apoptosis and Fas expression of astrocyte in patients with advanced ovarian cancer are higher than that in patients with Kourkenb disease The specificity of the local immunodeficiency in peritoneal cavity of primary ovarian cancer. (2) Effective treatment can reduce the apoptosis of T lymphocytes in peripheral blood of patients with ovarian cancer. (3) The Fas expression of T lymphocytes in ovarian cancer ascites is significantly increased, which is an important target of ovarian tumor immunotherapy. (4) CA125 can indirectly reflect the local immune status of ovarian cancer abdominal cavity.
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