[信号转导和转录激活因子2在卵巢癌中的高表达及其对卵巢癌细胞转移的影响]
[High expression of STAT2 in ovarian cancer and its effect on metastasis of ovarian cancer cells].
作者信息
Chen Xuan, Huang Jingying, Lü Yuchun
机构信息
Department of Obstetrics and Gynecology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 350005, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Jan 30;40(1):34-41. doi: 10.12122/j.issn.1673-4254.2020.01.06.
OBJECTIVE
To investigate the expression of signal transduction and activator of transcription 2 (STAT2) in ovarian cancer and its correlation with the prognosis of ovarian cancer patients and explore the role of STAT2 inregulating metastasis of ovarian cancer cells.
METHODS
RT-qPCR was performed to detect the expression of STAT2 mRNA in 62 fresh frozen ovarian cancer tissues and 62 normal ovarian tissues; immunohistochemistry was used to detect STAT2 protein expressions in 95 paraffin-embedded ovarian cancer samples and 33 normal ovarian tissues. Kaplan-Meier method was used to analyze the correlation between the expression of STAT2 and the prognosis of the patients. We also examined the relationship between STAT2 and the patients' prognosis by analyzing the data in Kaplan-Meier Plotter database. Western blotting was performed to detect the expression of STAT2 in different ovarian cancer cell lines. In A2780 cells with the highest STAT2 expression, we examined the effects of STAT2 interference on cell migration and invasiveness using Transwell migration assay and on the expressions of the downstream molecule epidermal growth factor receptor (EGFR).
RESULTS
Ovarian cancer tissues expressed significantly higher levels of STAT2 mRNA than normal ovarian tissue. A high STAT2 mRNA expression was correlated with an advanced FIGO stage. Immunohistochemistry showed that 67.4% of the ovarian cancer samples, as compared with 28.3% of normal ovarian tissues, showed high STAT2 expressions. In ovarian cancer patients, a high expression of STAT2 protein was associated with ascites volume, distant metastasis and FIGO stage ( < 0.05). Survival analysis showed that ovarian cancer patients with a high expression of STAT2 protein had poor overall survival (=0.021) and progression-free survival (=0.018). STAT2 was overexpressed in all the ovarian cancer cell lines tested, and A2780 cell lines showed the highest expression. Interference of STAT2 significantly suppressed the migration and invasiveness ( < 0.01) and lowered the expression level of EGFR in A2780 cells.
CONCLUSIONS
STAT2 is overexpressed in ovarian cancer. A high expression of STAT2 is associated with a poor prognosis of ovarian cancer patients. STAT2 may promote the metastasis of ovarian cancer by enhancing the expression of EGFR.
目的
探讨信号转导与转录激活因子2（STAT2）在卵巢癌中的表达及其与卵巢癌患者预后的相关性，并探究STAT2在调控卵巢癌细胞转移中的作用。
方法
采用RT-qPCR检测62例新鲜冰冻卵巢癌组织及62例正常卵巢组织中STAT2 mRNA的表达；采用免疫组织化学法检测95例石蜡包埋卵巢癌样本及33例正常卵巢组织中STAT2蛋白的表达。采用Kaplan-Meier法分析STAT2表达与患者预后的相关性。我们还通过分析Kaplan-Meier Plotter数据库中的数据来研究STAT2与患者预后的关系。采用蛋白质免疫印迹法检测不同卵巢癌细胞系中STAT2的表达。在STAT2表达最高的A2780细胞中，我们采用Transwell迁移实验检测STAT2干扰对细胞迁移和侵袭能力的影响，并检测下游分子表皮生长因子受体（EGFR）的表达。
结果
卵巢癌组织中STAT2 mRNA表达水平显著高于正常卵巢组织。STAT2 mRNA高表达与国际妇产科联盟（FIGO）分期较晚相关。免疫组织化学显示，67.4%的卵巢癌样本STAT2呈高表达，而正常卵巢组织中这一比例为28.3%。在卵巢癌患者中，STAT2蛋白高表达与腹水体积、远处转移及FIGO分期相关（P<0.05）。生存分析显示，STAT2蛋白高表达的卵巢癌患者总生存期（P=0.021）和无进展生存期（P=0.018）较差。STAT2在所检测的所有卵巢癌细胞系中均过表达，A2780细胞系表达最高。干扰STAT2可显著抑制A2780细胞的迁移和侵袭能力（P<0.01），并降低EGFR的表达水平。
结论
STAT2在卵巢癌中过表达。STAT2高表达与卵巢癌患者预后不良相关。STAT2可能通过增强EGFR的表达促进卵巢癌转移。
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