Cho Hanbyoul, Kim Sunghoon, Shin Ha-Yeon, Chung Eun Joo, Kitano Haruhisa, Hyon Park Jae, Park Lucienne, Chung Joon-Yong, Hewitt Stephen M, Kim Jae-Hoon
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Genes Chromosomes Cancer. 2014 Apr;53(4):277-88. doi: 10.1002/gcc.22136. Epub 2014 Feb 1.
Stress-induced phosphoprotein1 (STIP1) is a candidate biomarker in epithelial ovarian cancer (EOC). In this study, we investigated in detail the expression of STIP1, as well as its functions, in EOC. STIP1 expression was assessed by immunohistochemistry (IHC) and the results were compared with clinicopathologic factors, including survival data. The effects of STIP1 gene silencing via small interfering RNA (siRNA) were examined in EOC cells and a xenograft model. The expression of STIP1 protein in EOC was significantly higher than in the other study groups (P < 0.001), and this increase of expression was significantly associated with tumor stage (P = 0.005), tumor grade (P = 0.029), and lymph node metastasis (P = 0.020). In multivariate analysis, overall survival in EOC was significantly shorter in cases with high STIP1 expression (HR = 2.78 [1.01-7.63], P = 0.047). STIP1 silencing in EOC cells resulted in inhibition of cell proliferation and invasion. In addition, in vivo experiments using STIP1 siRNA clearly showed a strong inhibition of tumor growth and a modulation of expression of prosurvival and apoptotic genes, further suggesting that STIP1 silencing can prevent cell proliferation and invasion. In conclusion, increased STIP1 expression is associated with poor survival outcome in EOC, and STIP1 may represent a useful therapeutic target in EOC patients.
应激诱导磷蛋白1(STIP1)是上皮性卵巢癌(EOC)的一个候选生物标志物。在本研究中,我们详细调查了STIP1在EOC中的表达及其功能。通过免疫组织化学(IHC)评估STIP1的表达,并将结果与包括生存数据在内的临床病理因素进行比较。在EOC细胞和异种移植模型中检测了通过小干扰RNA(siRNA)沉默STIP1基因的效果。EOC中STIP1蛋白的表达显著高于其他研究组(P < 0.001),且这种表达增加与肿瘤分期(P = 0.005)、肿瘤分级(P = 0.029)和淋巴结转移(P = 0.020)显著相关。在多变量分析中,STIP1高表达的EOC患者总生存期显著缩短(HR = 2.78 [1.01 - 7.63],P = 0.047)。EOC细胞中STIP1沉默导致细胞增殖和侵袭受到抑制。此外,使用STIP1 siRNA的体内实验清楚地显示出对肿瘤生长的强烈抑制以及对生存相关基因和凋亡基因表达的调节,进一步表明STIP1沉默可阻止细胞增殖和侵袭。总之,STIP1表达增加与EOC患者的不良生存结果相关,STIP1可能是EOC患者的一个有用治疗靶点。