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LIM和SH3结构域蛋白1(LASP-1)的过表达与透明细胞肾细胞癌的侵袭性表型及不良预后相关。

LIM and SH3 domain protein 1 (LASP-1) overexpression was associated with aggressive phenotype and poor prognosis in clear cell renal cell cancer.

作者信息

Yang Fan, Zhou Xingchun, Du Shuangkuan, Zhao Yongjun, Ren Wei, Deng Qian, Wang Fuli, Yuan Jianlin

机构信息

Department of Urology Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.

出版信息

PLoS One. 2014 Jun 23;9(6):e100557. doi: 10.1371/journal.pone.0100557. eCollection 2014.

Abstract

BACKGROUND

LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein that is known to be involved in numerous biological and pathological processes. LASP-1 overexpression has been described in several types of cancers, but its expression and role in clear cell renal cell cancer (ccRCC) remains unknown.

METHODS

Using immunohistochemistry, we analyzed LASP-1 protein expression in 216 clinicopathologically characterized ccRCC cases. We also examined LASP-1 expression in 20 paired ccRCC tissues and in 2 cell lines by real-time PCR and Western blot. Using RNA interference, we investigated the effects of LASP-1 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine the associations between LASP-1 levels, tumor features and patient outcomes.

RESULTS

LASP-1 overexpression was observed in ccRCC tissues (P<0.0001) compared to adjuvant nontumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (P = 0.044 and 0.006, respectively) in patients with ccRCC. RNA interference-mediated silencing of the LASP-1 gene in 786-0 ccRCC cells significantly inhibited cell migration.

CONCLUSIONS

The results of the present study indicate that LASP-1 may serve as a prognostic biomarker for ccRCC patients and may be a promising target for the treatment of ccRCC.

摘要

背景

LIM和SH3结构域蛋白1(LASP-1)是一种特定的粘着斑蛋白,已知其参与众多生物学和病理学过程。在几种类型的癌症中均有LASP-1过表达的报道,但其在透明细胞肾细胞癌(ccRCC)中的表达及作用仍不清楚。

方法

我们采用免疫组织化学方法分析了216例具有临床病理特征的ccRCC病例中LASP-1蛋白的表达情况。我们还通过实时PCR和蛋白质印迹法检测了20对ccRCC组织及2种细胞系中LASP-1的表达。利用RNA干扰技术,我们研究了LASP-1缺失对体外肿瘤细胞行为的影响。采用统计学分析来确定LASP-1水平、肿瘤特征与患者预后之间的关联。

结果

与癌旁非肿瘤组织相比,在ccRCC组织中观察到LASP-1过表达(P<0.0001),并且其表达水平与ccRCC患者的总生存期和无复发生存期密切相关(分别为P = 0.044和0.006)。RNA干扰介导的786-0 ccRCC细胞中LASP-1基因沉默显著抑制了细胞迁移。

结论

本研究结果表明,LASP-1可能作为ccRCC患者的预后生物标志物,并且可能是ccRCC治疗的一个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e34b/4067378/1e07fff40a5e/pone.0100557.g001.jpg

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