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RAC2 可作为一种预后生物标志物,并促进肾透明细胞癌的进展。

RAC2 acts as a prognostic biomarker and promotes the progression of clear cell renal cell carcinoma.

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Int J Oncol. 2019 Sep;55(3):645-656. doi: 10.3892/ijo.2019.4849. Epub 2019 Jul 26.

Abstract

As one of the most commonly reported malignancies of the urinary system, clear cell renal cell carcinoma (ccRCC) is an advanced metastatic tumor with high mortality rates. The Rac family small GTPase 2 (RAC2) is a member of the Rho GTPases. Although Rho GTPases play an important role in numerous different types of tumor, whether they have functions in ccRCC remains uncertain. The present study utilized bioinformatics analyses in order to compare the expression levels of RAC2 in ccRCC tumors vs. adjacent tissues, and assessed the association between RAC2 expression and clinicopathological parameters. Furthermore, reverse transcription‑quantitative PCR, western blotting and immunohistochemistry assays were performed to validate RAC2 expression levels in human ccRCC tissues and cell lines. Functional experiments were also conducted in order to identify the roles of RAC2 in vitro. The results revealed that RAC2 was upregulated in ccRCC tissues and cell lines. In addition, elevated expression levels of RAC2 were significantly associated with a poor overall survival (P=0.0061), higher Tumor‑Node‑Metastasis stage and worse G grade. Receiver operating characteristic analysis indicated that high expression levels of RAC2 could be a diagnostic index for ccRCC (area under the curve, 0.9095; P<0.0001). Furthermore, knockdown of RAC2 in vitro attenuated the proliferation, migration and invasion of renal carcinoma cells. In conclusion, the results of the present study demonstrated that RAC2 may act as a promising prognostic and diagnostic biomarker of ccRCC, and could be considered as a potential therapeutic target for treating ccRCC.

摘要

作为泌尿系统最常见的恶性肿瘤之一,透明细胞肾细胞癌(ccRCC)是一种死亡率较高的晚期转移性肿瘤。Rac 家族小 GTP 酶 2(RAC2)是 Rho GTPases 的成员。尽管 Rho GTPases 在多种不同类型的肿瘤中发挥着重要作用,但它们在 ccRCC 中的功能仍不确定。本研究利用生物信息学分析比较了 ccRCC 肿瘤与相邻组织中 RAC2 的表达水平,并评估了 RAC2 表达与临床病理参数之间的关联。此外,还进行了逆转录定量 PCR、western blot 和免疫组织化学检测,以验证 RAC2 在人 ccRCC 组织和细胞系中的表达水平。还进行了功能实验,以鉴定 RAC2 在体外的作用。结果显示,RAC2 在 ccRCC 组织和细胞系中上调。此外,RAC2 的高表达水平与总生存率降低(P=0.0061)、肿瘤-淋巴结-转移分期较高和 G 分级较差显著相关。受试者工作特征分析表明,RAC2 的高表达水平可能是 ccRCC 的诊断指标(曲线下面积,0.9095;P<0.0001)。此外,体外敲低 RAC2 可减弱肾癌细胞的增殖、迁移和侵袭。综上所述,本研究结果表明,RAC2 可能作为 ccRCC 有前途的预后和诊断生物标志物,并可被视为治疗 ccRCC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a192/6685597/dabadabab20b/IJO-55-03-0645-g00.jpg

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