Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma
Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma
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DOI：
10.3892/or.2019.7352
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发表时间：
2019-12-01
期刊：
影响因子：
4.2
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Shimbo, Akiko;Kajiyama, Hiroaki;Kikkawa, Fumitaka
近年来，结缔组织生长因子(CTGF)被证明与多种恶性肿瘤的侵袭性特征有关，包括增殖、侵袭和转移。本研究旨在探讨CTGF在上皮性卵巢癌中的表达及作用，以阐明其分子机制及临床意义。对104例卵巢上皮性癌石蜡切片进行CTGF免疫组织化学染色，半定量检测染色阳性率。此外，我们还探讨了CTGF的表达在EOC细胞的迁移促进作用和化疗耐药中的作用。结果显示，104例卵巢癌组织中CTGF低表达65例(62.5%)，高表达39例(37.5%)。肿瘤生长因子水平高的患者无进展(PFS)和总生存率(OS)分别低于低水平组[PFS(对数等级：P=0.0076)和OS(对数等级：P=0.0078)]。多变量分析显示，结缔组织生长因子的表达是PFS和OS的显著预测因子[PFS：HR(高与低)：1.837，95%CI：1.023~3.289(P=0.0418)；OS：HR：2.141，95%CI：1.077~4.296(P=0.0300)]。在体外研究中，在获得性紫杉醇(PTX)耐药的EOC细胞中，CTGF表达的沉默导致PTX敏感性的恢复。此外，我们还证实了依赖于转化生长因子-β的细胞对CTGF缺失细胞的迁移促进作用被完全抑制。综上所述，本研究结果提示CTGF可能参与了EOC的迁移促进作用和化疗耐药，提示它可能是克服EOC恶性特性的一个靶点。
Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023-3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077-4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF-beta-dependent migration-promoting effect on these CTGF-depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration-promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC.