目的:Janus激酶(JAK)和信号转导和转录激活因子(STAT)的激活在卵巢高级别浆液性癌(HGSC)的预后和靶向治疗中起重要作用。利用简单可行的技术,本研究旨在评估卵巢HGSC患者JAK/STAT信号通路的激活,探讨JAK/STAT信号通路激活与HGSC患者预后的相关性。
方法:我们在73例卵巢HGSC患者的石蜡包埋载玻片上进行了磷酸化STAT3(pSTAT3)和磷酸化STAT5(pSTAT5)的免疫组织化学,并评估两种标志物的表达水平和范围。根据pSTAT3和pSTAT5的免疫染色分级评分,将73例卵巢HGSC分为STAT3低/高表达组和STAT5低/高表达组,并分析了不同组患者的预后,为了探讨pSTAT3和pSTAT5蛋白的表达与HGSC患者预后的关系。
结果:部分卵巢HGSC病例显示pSTAT3和pSTAT5蛋白高表达,这与HGSC患者预后较差有关。pSTAT3和pSTAT5的表达水平在预后较好(生存时间≥3年)和预后较差(生存时间<3年)患者间差异有统计学意义。pSTAT3、pSTAT5或这两种标志物蛋白表达较高的患者预后较差。无进展生存时间和总生存时间显著缩短(P<0.001)。
结论:pSTAT3和pSTAT5蛋白的免疫染色可能有助于评估和预测卵巢HGSC患者的预后。并确定可能对STAT抑制剂和抗血管生成疗法有更高反应机会的患者。
OBJECTIVE: The activation of Janus kinase (JAK) and signal transducers and activators of transcription (STAT) plays an important role in the prognosis and targeted therapy of ovarian high-grade serous carcinoma (HGSC). Utilizing simple and practicable technique, this study aimed to evaluate the activation of JAK/STAT signaling pathway in ovarian HGSC patients, and investigated the correlation between the activation of JAK/STAT signaling pathway and the prognosis of the HGSC patients.
METHODS: We performed immunohistochemistry of phosphorylated STAT3 (pSTAT3) and phosphorylated STAT5 (pSTAT5) on paraffin imbedded slides of 73 ovarian HGSC patients, and evaluated the expression level and range of both markers. According to the grading score of the immunostaining of pSTAT3 and pSTAT5, we divided the 73 ovarian HGSC cases into STAT3 low/high expression and STAT5 low/high expression groups, and analyzed the prognosis of the patients in different groups, in order to explore the relationship between the expression of pSTAT3 and pSTAT5 proteins and the prognosis of the HGSC patients.
RESULTS: Some of the ovarian HGSC cases showed high expression of pSTAT3 and pSTAT5 protein level, which was related to the poorer prognosis of the HGSC patients. There was a significant difference in the expression level of pSTAT3 and pSTAT5 between the patients with better prognosis (survival time ≥3 years) and poorer prognosis (survival time < 3 years). The patients with higher protein expression of pSTAT3, pSTAT5 or both markers might have poorer prognosis, with significant shorter progression-free survival time and overall survival time (P < 0.001).
CONCLUSIONS: Immunostaining of pSTAT3 and pSTAT5 proteins might be helpful to evaluate and predict the prognosis of the ovarian HGSC patients, and to identify the patients who might have higher chances to respond to the STAT inhibitors and anti-angiogenesis therapy.