南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (01): 34-41.doi: 10.12122/j.issn.1673-4254.2020.01.06

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STAT2在卵巢癌中表达升高并与卵巢癌患者生存不良有关

陈 萱，黄静莹，吕育纯   

  • 出版日期:2020-02-18 发布日期:2020-01-20

High expression of STAT2 in ovarian cancer and its effect on metastasis of ovarian cancer cells

  • Online:2020-02-18 Published:2020-01-20

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摘要： 目的 探讨信号转导及转录活化因子2（STAT2）在卵巢癌中的表达及与患者预后的相关性，并研究STAT2对卵巢癌细胞转移能力的影响和作用机制。方法 RT-qPCR分析62例新鲜冰冻卵巢癌组织和62例正常卵巢组织中STAT2的mRNA的表达，免疫组化法检测95例卵巢癌石蜡样本和33例正常卵巢石蜡样本中STAT2蛋白的表达，Kaplan-Meier法分析STAT2表达和患者的预后之间的相关性，分析Kaplan-Meier Plotter数据库中STAT2与患者预后之间的关系。Western blot检测STAT2在卵巢癌细胞株中的表达，在最高表达的A2780细胞株中干扰STAT2后，Transwell检测卵巢癌细胞迁移、侵袭能力的变化；以及下游分子EGFR表达水平的变化。结果 卵巢癌组织中STAT2 mRNA的表达高于正常卵巢组织，STAT2 mRNA表达与较差的FIGO分期相 关。免疫组化显示STAT2蛋白在卵巢癌组织中的高表达率为67.4%，高于正常卵巢组织的28.3%；卵巢癌患者中，STAT2蛋白的高表达与患者的腹水量、有无远处转移及FIGO分期相关（P<0.05）。生存分析表明高表达STAT2蛋白的卵巢癌患者的整体生存期 （P=0.021）及无进展生存期（P=0.018）较差。STAT2在卵巢癌细胞株中普遍呈高表达，A2780细胞株中表达最高，用于建立干扰细胞株；干扰STAT2后，A2780细胞迁移和侵袭能力减弱（P<0.01），并且下游分子EGFR的mRNA和蛋白表达水平较对照组均降低。 结论 STAT2在卵巢癌中表达升高，与卵巢癌患者预后不良相关，STAT2可能通过促进EGFR的表达而促进卵巢癌的转移。

Abstract: 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 (P<0.05). Survival analysis showed that ovarian cancer patients with a high expression of STAT2 protein had poor overall survival (P=0.021) and progression-free survival (P=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 (P<0.01) and lowered the expression level of EGFR in A2780 cells. Conclusion 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.