GPC3在卵巢透明细胞腺癌中的表达及临床意义
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国家自然科学基金青年基金(81201703)


Expression of glypican-3 and its clinical significance in ovarian clear cell adenocarcinoma
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    摘要:

    目的:探讨磷脂酰肌醇蛋白聚糖3(glypican-3,GPC3)在卵巢透明细胞腺癌中的表达及临床意义。方法:采用免疫组织化学方法分别检测83例卵巢癌组织(透明细胞腺癌45例-浆液性癌20例-黏液性癌18例)-20例浆液性囊腺瘤及20例正常卵巢组织中GPC3蛋白的表达情况,实时荧光定量PCR法检测38例卵巢癌组织(透明细胞腺癌20例-浆液性癌10例-黏液性癌8例)-5例浆液性囊腺瘤和5例正常卵巢组织中mRNA的表达情况,并分析GPC3与卵巢透明细胞腺癌临床病理学参数及预后的相关性。结果:①卵巢透明细胞腺癌中GPC3蛋白阳性表达率和mRNA表达量(82.2%;1.326 1 ± 0.493 6)均明显高于浆液性癌(20%;0.426 5 ± 0.029 4)-黏液性癌(5%;0.265 2 ± 0.103 9)-浆液性囊腺瘤(0%;0.141 3 ± 0.011 3)-正常卵巢组织(0%;0.291 4 ± 0.048 1),差异有统计学意义(P均 < 0.01);②GPC3蛋白阳性表达率及GPC3 mRNA表达量与卵巢透明细胞腺癌的临床分期有相关性,Ⅲ~Ⅳ期患者中的表达(100%;1.808 1 ± 0.265 7)显著高于Ⅰ~Ⅱ期患者(71.4%; 1.045 8 ± 0.403 6)(P值 < 0.01);③卵巢透明细胞腺癌铂类药物耐药患者GPC3蛋白阳性表达率及mRNA表达量(100%; 1.808 1 ± 0.265 7)均高于铂类药物敏感型患者(70.3%; 0.991 8 ± 0.330 3)(P < 0.05);④GPC3蛋白阳性表达率与卵巢透明细胞腺癌患者的预后相关,预后差的患者中阳性率及表达量高,差异有统计学意义(P < 0.05),Kaplan-Meier单因素生存分析亦显示GPC3蛋白为影响预后的因素(P=0.048);⑤卵巢透明细胞腺癌中GPC3蛋白阳性表达率和mRNA表达量与患者的淋巴结转移和远处器官转移无相关性(P > 0.05)。结论:GPC3在病理鉴别诊断中有重要意义,GPC3与卵巢透明细胞腺癌患者的临床分期和铂类耐药相关,提示其可能在卵巢透明细胞腺癌的发生发展起重要作用,有望成为卵巢透明细胞腺癌的预后指标和潜在治疗靶标。

    Abstract:

    Objective:To investigate the expression of glypican-3 (GPC3)protein and mRNA in ovarian clear cell adenocarcinoma and its correlation with clinical pathologic parameters. Methods:The expression of GPC3 protein was detected by immunohistochemistry in 83 cases of ovarian cancer including 45 clear cell adenocarcinoma,20 serous cystadenocarcinoma,18 mucinous cystadenocarcinoma,20 cases of serous cystadenoma and 20 cases of normal ovary. The expression of GPC3 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction (RT-PCR) in 20 clear cell adenocarcinoma,10 serous cystadenocarcinoma,8 mucinous cystadenocarcinoma, 5 serous cystadenoma and 5 normal ovary tissues. The correlation between GPC3 expression and relative clinical pathologic parameters was analyzed. Results:①In ovarian clear cell adenocarcinoma, the positive rate of GPC3 protein and the mRNA expression (82.2%;1.326 1 ± 0.493 6) were significantly higher than those in ovarian serous cystadenocarcinoma (20%;0.426 5 ± 0.029 4),mucinous cystadenocarcinoma (5%; 0.265 2 ± 0.103 9),serous cystadenoma (0; 0.141 3 ± 0.011 3) and normal ovarian tissue (0; 0.291 4 ± 0.048 1)(P < 0.01); ②Both the expression of GPC3 protein and the mRNA were relevant to the clinical stage of ovarian clear cell adenocarcinoma. GPC3 expression in stage Ⅲ or Ⅳ (100%;1.808 1 ± 0.265 7) was significantly higher than that in stage Ⅰ or Ⅱ (71.4%;1.045 8 ± 0.403 6) (P <0.01) ;③Both the expression of GPC3 protein and mRNA were relevant to the status of cisplatin resistance. GPC3 expression in cisplatin-resistant patients (100%;1.808 1 ± 0.265 7) was higher than that in cisplatin-sensitive patients (70.3%;0.991 8 ± 0.330 3) (P < 0.05);④GPC3 protein expression was associated with survival of clear cell adenocarcinoma,which was higher in patients with poor prognosis (P < 0.05). Kaplan-Meier analysis showed that GPC3 protein expression was a prognostic factor (P=0.048);⑤GPC3 protein expression in ovarian clear cell adenocarcinoma had no relavance with the lymph node metastasis or distant metastasis (P > 0.05). Conclusion:GPC3 has an important significance in the differential diagnosis. There was a significant relationship between GPC3 expression and clinical stage and cisplatin resistance in ovarian clear cell adenocarcinoma. GPC3 may play an important role in the development of ovarian clear cell adenocarcinoma and could be used as a helpful prognostic marker and potential target .

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李雪洁,李红霞,李 霄,宋国新,张炜明,张智弘. GPC3在卵巢透明细胞腺癌中的表达及临床意义[J].南京医科大学学报(自然科学版),2015,(5):631-637

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  • 收稿日期:2015-01-13
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  • 在线发布日期: 2015-05-22
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