TTK与肾透明细胞癌的临床病理特征及患者预后的相关性分析

TTK contributes to tumor growth and metastasis of clear cell renal cell carcinoma by inducing cell proliferation and invasion

目的探讨TTK在肾透明细胞癌(ccRCC)组织中的表达水平及其与ccRCC患者临床病理特征和预后的相关性,并研究TTK在ccRCC进展中的潜在作用。方法对112例ccRCC标本及其对应的癌旁正常组织行免疫组织化学(IHC)测定,根据TTK表达水平将患者分为TTK高表达组和TTK低表达组。分析患者年龄、性别和分期等临床特征与TTK表达水平的相关性。分别通过集落形成实验和Transwell实验检测TTK对ccRCC细胞增殖和侵袭的影响,并通过动物实验观察TTK对肿瘤生长和转移的影响。结果 ccRCC患者标本中TTK表达水平明显升高。TTK表达水平与患者T分期(P=0.008)和淋巴结转移(P=0.023)明显相关。TTK敲除能够抑制ccRCC细胞株HTB-47和CRL-1932的增殖和侵袭能力,还有助于小鼠体内ccRCC的生长和转移。结论 TTK能够影响ccRCC的进展,并可能成为ccRCC治疗的新靶点。

Objective To determine the expression levels of TTK in clear cell renal cell carcinoma(ccRCC)tissues and its possible link with the clinical palhologic characteristics and the prognosis of patients undergoing this disease,and further explore the potential role of TTK in the progression of ccRCC.Methods Immunohistochemical(IHC)assays were performed to detect the expression levels of TTK in 112 samples of ccRCC tissues and corresponding non-tumor tissues.According to the results of IHC assays,patients were divided into TTK high expression and low expression group.Clinical analysis related to the clinical features(age,gender,T stage),and the potential link between TTK expression levels and clinical features were analyzed.In addition,the effects of TTK on the proliferation and invasion of ccRCC cells were detected with colony formation assay and transwell assays,respectively.The possible effects of TTK on tumor growth and metastasis were measured in mice.Results We found a high expression level of TTK in human ccRCC tissues from patients who received surgical treatment.We also found its expression level was obviously associated with clinical characteristics,such as F stage(P=0.008)and lymphatic metastasis(P=0.023).We further confirmed that knockdown of TTK suppressed cell proliferation and invasion in 2 types of ccRCC cells,HTB-47 and CRL-1932 cells.Conclusions TTK can affect the progression of ccRCC and we can further mechanically confirm that it can be a novel therapeutic target for the treatment of ccRCC.