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BTG3表达降低与卵巢癌的发生、侵袭性及预后相关。

Decreased expression of BTG3 was linked to carcinogenesis, aggressiveness, and prognosis of ovarian carcinoma.

作者信息

Deng Boya, Zhao Yang, Gou Wenfeng, Chen Shuo, Mao Xiaoyun, Takano Yasuo, Zheng Huachuan

机构信息

Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.

出版信息

Tumour Biol. 2013 Oct;34(5):2617-24. doi: 10.1007/s13277-013-0811-2. Epub 2013 May 9.

Abstract

B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT-PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p < 0.05), and was negatively correlated with dedifferentiation and FIGO staging of EOC (p < 0.05). Using western blot, BTG3 protein was found lower in EOCs compared to the normal and benign tumors (p < 0.05), and poorly differentiated EOCs showed lower BTG3 expression than well-differentiated and moderately differentiated EOCs (p < 0.05). Immunohistochemically, BTG3 protein expression was statistically lower in EOCs than normal tissue and benign tumors (p < 0.05). EOC patients with low BTG3 protein expression showed a higher incidence of metastasis (p = 0.020), poor differentiation (p = 0.030), and shorter disease-free time and overall survival time (p < 0.05). By using Cox's proportional hazard model, BTG3 protein expression and FIGO staging were independent prognostic factors for both disease-free time and overall survival time of EOCs (p < 0.05). It was suggested that down-regulated BTG3 expression might play roles in the pathogenesis and aggressiveness of EOC. BTG3 protein expression may be considered as a good marker to indicate the favorable prognosis of EOCs.

摘要

B细胞易位基因3(BTG3)是BTG家族的成员之一,该家族可抑制细胞增殖、转移和血管生成,还能调节多种细胞类型的细胞周期进程和分化。然而,尚无研究分析BTG3在上皮性卵巢癌(EOC)中的表达情况。在此,我们研究了BTG3在EOC发生及后续进展过程中的表达情况。通过实时逆转录聚合酶链反应(RT-PCR)检测卵巢良性和恶性肿瘤中BTG3 mRNA的表达。采用免疫组织化学方法检测包含卵巢正常组织、良性和交界性上皮性卵巢肿瘤以及EOC的组织芯片上BTG3蛋白的表达。对BTG3与EOC临床病理及预后的关系进行统计学分析。还通过蛋白质印迹法评估卵巢正常组织、良性肿瘤和EOC中BTG3蛋白的表达。BTG3 mRNA表达水平在卵巢正常组织和良性肿瘤中高于交界性、原发性和转移性癌(p < 0.05),且与EOC的去分化及国际妇产科联盟(FIGO)分期呈负相关(p < 0.05)。蛋白质印迹法结果显示,与正常和良性肿瘤相比,EOC中BTG3蛋白含量较低(p < 0.05),低分化EOC的BTG3表达低于高分化和中分化EOC(p < 0.05)。免疫组织化学结果表明,EOC中BTG3蛋白表达在统计学上低于正常组织和良性肿瘤(p < 0.05)。BTG3蛋白表达低的EOC患者转移发生率更高(p = 0.020),分化差(p = 0.030),无病生存期和总生存期更短(p < 0.05)。通过Cox比例风险模型分析,BTG3蛋白表达和FIGO分期是EOC无病生存期和总生存期的独立预后因素(p < 0.05)。提示BTG3表达下调可能在EOC的发病机制和侵袭性中起作用。BTG3蛋白表达可被视为提示EOC预后良好的一个良好标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14ec/3785705/fd8d93305841/13277_2013_811_Fig1_HTML.jpg

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