BACKGROUND:To investigate the expression and function of RSK4, MMP-9 and CD44 in primary clear cell renal cell carcinoma (primary ccRCC) and metastatic clear cell renal cell carcinoma (metastatic ccRCC), as well as the correlation with clinicopathological features of patients.METHOD:The expression levels of RSK4, CD44 and MMP-9 in 52 primary ccRCC samples and 48 metastatic ccRCC samples were detected by immunohistochemistry, and the relationship between RSK4, CD44 and MMP-9 expression and clinicopathological features as well as prognosis of metastatic ccRCC patients was statistically analysed. Ectopic RSK4 expression in ccRCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.RESULTS:The positive rates of RSK4, MMP-9 and CD44 expression in metastatic ccRCC tissues were 75, 68.75 and 91.7%, respectively, while the rates in primary ccRCC tissues were 44.2, 34.6 and 69.2%, respectively. Thus, the positive rates in metastatic ccRCC were higher than those in primary ccRCC (P RSK4 ?=?0. 002; P MMP-9 ?=?0. 002; P CD44 ?=?0. 001). However, the expression of RSK4, CD44 and MMP-9 was unrelated to age, gender, or metastatic sites (P??0.05) but was related to WHO/ISUP nucleolar grade (P RSK4 ?=?0.019; P CD44 ?=?0.026; P MMP-9 ?=?0.049). In metastatic ccRCC, expression among the three proteins showed a positive correlation (P?=?0.008). Moreover, expression between RSK4 and CD44 (P?=?0.019) and MMP-9 and CD44 (P?=?0.05) also showed positive correlations, whereas RSK4 and MMP-9 showed no significant correlation (P?=?1.00). Molecular studies showed that overexpression of RSK4 could enhance the invasive and migratory abilities of ccRCC cell lines through the regulation of CD44 and MMP-9 expression and vice versa.CONCLUSIONS:The overexpression of RSK4, MMP-9 and CD44 is associated with the invasion and metastasis of ccRCC, indicating that they could be potential prognostic factors and serve as new potential therapeutic targets for ccRCC.
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机译：背景：探讨RSK4，MMP-9和CD44在初级透明细胞肾细胞癌（原发性CCRCC）和转移性透明细胞肾细胞癌（转移性CCRCC）中的表达和功能，以及与患者的临床病理特征的相关性。方法：通过免疫组织化学检测RSK4，CD44和MMP-9中的RSK4，CD44和MMP-9的表达水平，RSK4，CD44和MMP-9表达和临床病理特征的关系以及转移性CCRCC的预后患者在统计学分析。进行CCRCC细胞系中的异位RSK4表达以确定其对细胞周期调节，肿瘤侵袭性和转移能力的影响。结果：转移性CCRCC组织中RSK4，MMP-9和CD44表达的阳性率为75,68.75和91.7％分别分别为初级CCRCC组织的率分别为44.2,34.6和69.2％。因此，转移性CCRCC的阳性率高于初级CCRCC（P RSK4 = 0.002; P MMP-9？=Δ0.002; P CD44？= 0.001）。然而，RSK4，CD44和MMP-9的表达与年龄，性别或转移性位点无关（p？> 0.05），但与世卫组织/ isp核仁级有关（p rsk4？= 0.019; p cd44？= ？0.026; p mmp-9？=？0.049）。在转移性CCRCC中，三种蛋白质中的表达显示出阳性相关性（P？= 0.008）。此外，RSK4和CD44之间的表达（P？= 0.019）和MMP-9和CD44（P？= 0.05）也显示出阳性相关性，而RSK4和MMP-9显示出没有显着的相关性（P？= 1.00）。分子研究表明，RSK4的过表达可以通过CD44和MMP-9表达的调节增强CCRCC细胞系的侵袭性和迁移能力，反之亦然：结论：RSK4，MMP-9和CD44的过表达与侵袭相关CCRCC转移，表明它们可能是潜在的预后因素，并用作CCRCC的新潜在治疗靶标。
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