Shang An-Quan, Wu Jian, Bi Feng, Zhang Yu-Jie, Xu Lei-Rong, Li Ling-Ling, Chen Fei-Fei, Wang Wei-Wei, Zhu Jian-Jun, Liu You-Yi
a Clinical Medicine School , Ningxia Medical University , Yinchuan , P.R. China.
b Department of Laboratory Medicine , The Sixth People's Hospital of Yancheng City , Yancheng , P.R. China.
Cancer Biol Ther. 2017 May 4;18(5):314-322. doi: 10.1080/15384047.2017.1310343. Epub 2017 Apr 27.
The study aims to explore the relationship between expressions of HER2 and JAK/STAT3-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer (OC).
A total of 136 OC patients were collected. Immunohistochemistry was applied to measure the expressions of STAT3, p-STAT3, SOCS3, HER2 and p-HER2 in the tumor tissues and adjacent normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of HER2, SOCS3 and STAT3 and western blotting was applied for protein expressions of HER2, p-HER2, SOCS3, STAT3 and p-STAT3 in the tumor tissues and adjacent normal tissues. Flow cytometry was used for the cell apoptosis in the blank, afatinib (A), ruxolitinib (R) and afatinib + ruxolitinib (A + R) groups. Follow-up was performed to explore relationship of HER2, SOCS3, and STAT3 expressions with survival time of OC patients.
HER2, p-HER2, STAT3, and p-STAT3 expressions were higher while SOCS3 expression was lower in the tumor tissues. The positive expressions of STAT3, HER2, p-HER2 and p-STAT3 were lower while the positive expression of SOCS3 was higher in the adjacent normal tissues. The expressions of HER2, SOCS3, and p-STAT3 were associated with clinical stage and lymph node metastasis (LNM), and STAT3 expression has correlation with histological grade and LNM. The mRNA and protein expressions of HER2, STAT3 and p-STAT3 in the tumor tissues were higher than those in the adjacent normal tissues, but SOCS3 expression was significantly decreased. The positive expressions of HER2, p-HER2 and STAT3, the negative expression of SOCS3 and pathological stages were important risk factors for the prognosis of patients with OC.
Our study showed that the expressions of HER2, STAT3, and SOCS3 are associated with the progression of OC, and higher expressions of HER2 and STAT3 and lower expression of SOCS3 predict poor prognosis of OC.
本研究旨在探讨HER2与JAK/STAT3-SOCS3信号通路的表达与卵巢癌（OC）临床病理特征及预后的关系。
共收集136例OC患者。采用免疫组织化学法检测肿瘤组织及癌旁正常组织中STAT3、p-STAT3、SOCS3、HER2和p-HER2的表达。采用定量实时聚合酶链反应（qRT-PCR）检测肿瘤组织及癌旁正常组织中HER2、SOCS3和STAT3的mRNA表达，采用蛋白质印迹法检测肿瘤组织及癌旁正常组织中HER2、p-HER2、SOCS3、STAT3和p-STAT3的蛋白表达。采用流式细胞术检测空白组、阿法替尼（A）组、鲁索替尼（R）组及阿法替尼+鲁索替尼（A+R）组的细胞凋亡情况。进行随访以探讨HER2、SOCS3和STAT3表达与OC患者生存时间的关系。
肿瘤组织中HER2、p-HER2、STAT3和p-STAT3表达较高，而SOCS3表达较低。癌旁正常组织中STAT3、HER2、p-HER2和p-STAT3的阳性表达较低，而SOCS3的阳性表达较高。HER2、SOCS3和p-STAT3的表达与临床分期和淋巴结转移（LNM）相关，STAT3表达与组织学分级和LNM相关。肿瘤组织中HER2、STAT3和p-STAT3的mRNA和蛋白表达高于癌旁正常组织，但SOCS3表达显著降低。HER2、p-HER2和STAT3的阳性表达、SOCS3的阴性表达及病理分期是OC患者预后的重要危险因素。
我们的研究表明，HER2、STAT3和SOCS3的表达与OC的进展相关，HER2和STAT3的高表达及SOCS3的低表达预示OC预后不良。
