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[上皮性卵巢癌患者腹腔液及外周血T淋巴细胞凋亡与Fas表达及其与CA125关系的研究]

[Study of apoptosis and Fas expression of peritoneal fluid and peripheral blood T lymphocytes in patients with epithelial ovarian cancer and their relationship with CA125].

作者信息

Ma Ya-Xi, Ye Feng, Chen Huai-Zeng, Lü Wei-Guo, Xie Xing

机构信息

Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Mar 20;87(11):734-9.

PMID:17565840
Abstract

OBJECTIVE

To investigate the apoptosis and Fas (CD95) expression of T lymphocytes from the peripheral blood and peritoneal fluid of the patients with ovarian cancer and their relationship with CA125.

METHODS

Apoptosis and Fas expression of peritoneal fluid and peripheral blood T lymphocytes were assessed by flow cytometry. Peripheral blood samples were obtained from the following objects respectively: patients with stage III - IV ovarian cancer (n = 18) before and after treatment, patients with stage I - II ovarian cancer (n = 15), patients with benign ovarian tumor (n = 18), patients with Krukenberg tumor (n = 6) and normal control (n = 20). Peritoneal fluids were obtained from all the patients with ovarian cancer, Krukenberg tumor and ten patients with benign ovarian tumor. Level of serum CA125 of the patients with ovarian cancer was assessed.

RESULTS

In the patients with stage III - IV ovarian cancer, the apoptosis level of the peripheral blood T lymphocytes was 5.55 (3.57 - 9.62)%, significantly higher than those from the patients with stage I - II ovarian cancer, patients with benign ovarian tumor, controls (P < 0.008 in all instances) and the patients with stage III - IV ovarian cancer after treatment (P < 0.05). The intensity of Fas expression of the peripheral blood T lymphocytes from the patients with stage III - IV ovarian cancer was 51 +/- 10, significantly higher than that from controls (P < 0.05). In peritoneal fluid, the apoptosis rates of T lymphocytes, positive rate and intensity of Fas expression on T lymphocytes from patients with stage I - II and stage III - IV ovarian cancer were 17.41 (7.06 - 24.56)%, (57 +/- 16)%, (55 +/- 11)% and 34.06 (17.03 - 44.65)%, (66 +/- 12)%, (70 +/- 24)%, respectively, increased significantly compared with those from patients with benign ovarian tumor, which were 0.78 (0.67 - 1.44)%, (37 +/- 6)%, 43 +/- 6, respectively (P < 0.01 in all instances). The apoptosis level and positive rate of Fas expression on peritoneal fluid T lymphocytes from patients with stage III - IV ovarian cancer were significantly higher than those from patients with Krukenberg tumor (P < 0.01). There was a positive correlation between the serum CA125 level and the apoptosis level of peritoneal fluid T cell in the patients with stage I - II ovarian cancer (r = 0.77, P = 0.009). For ovarian cancer, the apoptosis level of peritoneal fluid T lymphocytes from patients with the serum CA125 > 500 KU/L was higher than that from the patients with the serum CA125 < or = 500 KU/L (P = 0.009).

CONCLUSIONS

(1) Extraordinarily increased apoptosis of T cells may play an important role in the development of systemic and celiac immunodeficiency in the patients with ovarian cancer. In contrast with the patients with Krukenberg tumor, the patients with advanced ovarian cancer hare higher percentage of apoptotic peritoneal fluid T lymphocytes, which shows the particularity of local immunity defect. (2) For the patients with ovarian cancer, efficient treatment can decrease the percentage of apoptotic peripheral blood T lymphocytes. (3) The increased positive rate and intensity of Fas expression on peritoneal fluid T lymphocytes stressed the significance of Fas interference in the treatment of ovarian cancer. (4) Level of serum CA125 can reflect the celiac immunity defection in patients with ovarian cancer.

摘要

目的

探讨卵巢癌患者外周血及腹水中T淋巴细胞凋亡及Fas(CD95)表达情况及其与CA125的关系。

方法

采用流式细胞术检测腹水及外周血T淋巴细胞凋亡及Fas表达。外周血样本分别取自以下对象:Ⅲ - Ⅳ期卵巢癌患者(n = 18)治疗前后、Ⅰ - Ⅱ期卵巢癌患者(n = 15)、卵巢良性肿瘤患者(n = 18)、库肯勃瘤患者(n = 6)及正常对照者(n = 20)。所有卵巢癌、库肯勃瘤患者及10例卵巢良性肿瘤患者均留取腹水。检测卵巢癌患者血清CA125水平。

结果

Ⅲ - Ⅳ期卵巢癌患者外周血T淋巴细胞凋亡水平为5.55(3.57 - 9.62)%,显著高于Ⅰ - Ⅱ期卵巢癌患者、卵巢良性肿瘤患者、对照者(均P < 0.008)及Ⅲ - Ⅳ期卵巢癌治疗后患者(P < 0.05)。Ⅲ - Ⅳ期卵巢癌患者外周血T淋巴细胞Fas表达强度为51±10,显著高于对照者(P < 0.05)。腹水中,Ⅰ - Ⅱ期及Ⅲ - Ⅳ期卵巢癌患者T淋巴细胞凋亡率、Fas表达阳性率及表达强度分别为17.41(7.06 - 24.56)%、(57±16)%、(55±11)%和34.06(17.03 - 44.65)%、(66±12)%、(70±24)%,与卵巢良性肿瘤患者相比均显著升高,后者分别为0.78(0.67 - 1.44)%、(37±6)%、43±6(均P < 0.01)。Ⅲ - Ⅳ期卵巢癌患者腹水中T淋巴细胞凋亡水平及Fas表达阳性率显著高于库肯勃瘤患者(P < 0.01)。Ⅰ - Ⅱ期卵巢癌患者血清CA125水平与腹水中T淋巴细胞凋亡水平呈正相关(r = 0.77,P = 0.009)。对于卵巢癌患者,血清CA125>500 KU/L者腹水中T淋巴细胞凋亡水平高于血清CA125≤500 KU/L者(P = 0.009)。

结论

(1)T细胞凋亡异常增加可能在卵巢癌患者全身及腹腔免疫缺陷的发生中起重要作用。与库肯勃瘤患者相比,晚期卵巢癌患者腹水中T淋巴细胞凋亡比例更高,显示出局部免疫缺陷的特殊性。(2)对于卵巢癌患者,有效治疗可降低外周血T淋巴细胞凋亡比例。(3)腹水中T淋巴细胞Fas表达阳性率及表达强度增加强调了Fas干预在卵巢癌治疗中的意义。(4)血清CA125水平可反映卵巢癌患者腹腔免疫缺陷情况。

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