中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (4): 260-268.doi: 10.3969/j.issn.1007-3969.2015.04.004

• 论著 • 上一篇    下一篇

CXXC指蛋白5在上皮性卵巢癌中的表达及其临床意义

汪景灏1,2,任渊3,张蓉1,2,韩英2,盛友华4,侯文静2,敖洪峰4   

  1. 1. 南方医科大学第三临床医学院,广东 广州 510665 ;
    2. 南方医科大学附属奉贤医院妇产科,上海 奉贤 201499 ;
    3. 常州市妇幼保健院妇产科,江苏 常州 213003 ;
    4. 南方医科大学附属奉贤医院病理科,上海 奉贤 201499
  • 出版日期:2015-04-30 发布日期:2015-05-25
  • 通信作者: 张蓉 E-mail:rongzhang@163.com

Effects of CXXC finger protein 5 up-regulated expression in epithelial ovarian cancer

WANG Jinghao1,2, REN Yuan3, ZHANG Rong1,2, HAN Ying2, SHENG Youhua4, HOU Wenjing2, AO Hongfeng4   

  1. 1.The Third Clinical Medical College of Southern Medical University, Guangzhou Guangdong 510665, China; 2.Department of Obstetrics and Gynecology, Fengxian Hospital, Southern Medical University, Shanghai 201400, China; 3.Department of Obstetrics and Gynecology, Changzhou Maternal and Child Care Hospital, Changzhou Jiangsu 213003, China; 4.Department of Pathology, Fengxian Hospital, Southern Medical University, Shanghai 201400, China
  • Published:2015-04-30 Online:2015-05-25
  • Contact: ZHANG Rong E-mail: rongzhang@163.com

摘要:    背景与目的:上皮性卵巢癌是最常见的卵巢肿瘤类型,发病率高,治疗效果不满意,生存率低。CXXC指蛋白5(CXXC finger protein 5,CXXC5)在上皮性卵巢癌中的研究鲜见报道,该研究通过对CXXC5在上皮性卵巢癌中的表达和对上皮性卵巢癌细胞功能的研究,旨在探讨CXXC5在上皮性卵巢癌中可能的作用和临床意义。方法:①通过肿瘤基因图集(The Cancer Genoma Atlas,TCGA)数据库提供的数据分析CXXC5在上皮性卵巢癌基因组中的变异;②通过免疫组织化学法(immunohistochemistry,IHC)检测CXXC5在上皮性卵巢癌组织芯片中的表达情况,并分析CXXC5的表达与临床病理特征之间的关系;③通过蛋白[质]印迹法(Western blot)和实时定量PCR(real-time quantitative PCR,qRT-PCR)检测CXXC5在5株上皮性卵巢癌细胞系中的表达情况,选取表达量最高的ES-2细胞株;④使用慢病毒包装质粒转染ES-2细胞株,经嘌呤霉素筛选后构建稳定转染干扰细胞株;使用细胞计数试剂盒(cell counting kit-8,CCK8)检测细胞增殖能力的变化。结果:①CXXC5在TCGA提供的上皮性卵巢癌基因组中以表达为主;②CXXC5在上皮性卵巢和卵巢良性上皮性囊肿中的高表达率分别为39.3%和13.5%,差异有统计学意义(P=0.003);CXXC5在浆液性卵巢癌、黏液性卵巢癌、子宫内膜样卵巢癌和卵巢透明细胞癌中的高表达率分别为43.0%、22.9%、23.5%和66.7%,两两比较差异均有统计学意义(P均=0.014);CXXC5在有淋巴结转移和无淋巴结转移的上皮性卵巢癌中表达率为60.0%和35.8%,差异有统计学意义(P=0.022);③CXXC5稳定干扰后,卵巢癌透明细胞株ES-2的增殖能力明显减弱,差异有统计学意义(P<0.05)。结论:CXXC5基因可能有促进卵巢癌细胞增殖的作用,可能是上皮性卵巢癌预后不良的生物标志物。

关键词:  CXXC指蛋白5, 上皮性卵巢癌, 组织微阵列, 免疫组织化学, 增殖

Abstract:     Background and purpose: Epithelial ovarian cancer has the highest mortality rate of gynecologic cancers and overall survival rates have improved little in the last 20 to 30 years. CXXC finger protein 5 (CXXC5) plays an important role in AML (acute myeloid leukemia) and MDS (myelodysplasia). However, little is known about its clinical significance and biological function in epithelial ovarian cancer. This study aimed to investigate the expression of the CXXC5 in ovarian cancer and the effect of the CXXC5 on ES-2 cell proliferation. Methods: ①The alteration of CXXC5 in cancer genomics data of TCGA (Cancer Genome Atlas) was analyzed. ②The CXXC5 protein in the tissue chips was detected containing 37 benign ovarian cyst and 173 malignant tumor samples. The relationship between the expression of the CXXC5 with the clinicopathological features of patients with ovarian cancer was analyzed by SPSS software; ③The cells with the highest CXXC5 expression quantity from 5 ovarian cancer cells were selected by real- time quantitative PCR (qRT-PCR) and Western blot. ④ES-2 cells with shRNA stable transfection were construted using the strategy of lentivirus infection and analyzed cell proliferation by cell counting kit-8(CCK8). Results: ①Through the TCGA database, CXXC5 amplification was found in 7 of 563 cases. ②The CXXC5 expression in ovarian malignant carcinoma (39.3%) was higher than that in benign ovarian cyst (13.5%, P=0.003), the histologic type was highly associated with CXXC5 (43% in serous, 22.9% in mucinous, 23.5% in endometrioid, 67% in clear cell, P=0.014) and there was a significant correlation between CXXC5 and lymph node metastasis (positive vs negative, P=0.022). ③The ES-2 cells with shRNA stable transfection had a growth disadvantage (P<0.05). Conclusion: The CXXC5 gene might have an advantage in proliferation of epithelial ovarian carcinoma and be expected to become the biomarker of poor prognosis.

Key words: CXXC finger protein 5, Epithelial ovarian cancer, Tissue microarray, Immunohistochemistry, Proliferation