Zhang Qian, Chen Wen-Ming, Zhang Xin-Xin, Zhang Hu-Xiang, Wang Han-Chu, Zheng Fei-Yun, Zhu Fang-Fang
Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2017 Mar;37(3):1826-1832. doi: 10.3892/or.2017.5429. Epub 2017 Feb 7.
Ovarian cancer is recognized as one of the worst gynecologic malignancies associated with rapid metastasis and poor overall survival rate. The identified valuable molecular biomarkers criticize importance of timely diagnosis for ovarian cancer. Salusin-β levels are dramatically increased in women with polycystic ovarian syndrome. However, the roles of salusin-β in ovarian cancer have yet to be fully elucidated. A total of 57 paired ovarian cancer specimens and matched adjacent normal tissues were used to measure the salusin-β levels. The prognostic value of salusin-β for tumor progression and survival rate was investigated. The effects of salusin-β on ovarian cancer cell proliferation and epithelial-mesenchymal transition were also explored. The expression of salusin-β was significantly increased in ovarian cancer tissue specimens compared with matched normal adjacent tissue (P<0.05). The high salusin-β level was closely related with FIGO stage and lymph node metastases. The ovarian cancer patients with high salusin-β had a shorter overall survival (P<0.05). Salusin-β obviously enhanced the proliferation and epithelial mesenchymal-transition of SKOV3 cells. Furthermore, salusin-β substantially decreased the expression of p-GSK-3β and GSK-3β, but stimulated the β-catenin expression and downstream genes of wnt/β-catenin including cyclin D1 and C-myc. Our data demonstrated for the first time that upregulated salusin-β may be a novel independent prognostic biomarker for overall survival of ovarian cancer. Salusin-β accelerated the proliferation and epithelial mesenchymal transition of ovarian cancer cells at least partly via activation of Wnt/β-catenin signaling pathway. Salusin-β may be an important target for therapeutic intervention in ovarian cancer.
卵巢癌被认为是最严重的妇科恶性肿瘤之一,具有快速转移和总体生存率低的特点。已确定的有价值的分子生物标志物凸显了卵巢癌及时诊断的重要性。多囊卵巢综合征女性的Salusin-β水平显著升高。然而,Salusin-β在卵巢癌中的作用尚未完全阐明。本研究共使用57对卵巢癌标本及其匹配的相邻正常组织来测量Salusin-β水平。研究了Salusin-β对肿瘤进展和生存率的预后价值。还探讨了Salusin-β对卵巢癌细胞增殖和上皮-间质转化的影响。与匹配的正常相邻组织相比,卵巢癌组织标本中Salusin-β的表达显著增加(P<0.05)。高Salusin-β水平与国际妇产科联盟(FIGO)分期和淋巴结转移密切相关。Salusin-β水平高的卵巢癌患者总生存期较短(P<0.05)。Salusin-β明显增强了SKOV3细胞的增殖和上皮间质转化。此外,Salusin-β显著降低了p-GSK-3β和GSK-3β的表达,但刺激了β-连环蛋白的表达以及wnt/β-连环蛋白的下游基因,包括细胞周期蛋白D1和C-myc。我们的数据首次表明,上调的Salusin-β可能是卵巢癌总生存期的一种新型独立预后生物标志物。Salusin-β至少部分通过激活Wnt/β-连环蛋白信号通路加速了卵巢癌细胞的增殖和上皮间质转化。Salusin-β可能是卵巢癌治疗干预的一个重要靶点。