Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial-mesenchymal transition.

Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial-mesenchymal transition.
复制标题

DOI:
10.1111/jcmm.12158
复制
发表时间:
2014-01
影响因子:
5.3
通讯作者:
Hong J
Hong J
中科院分区:
医学2区
文献类型:
--
作者:
He L;Zhou X;Qu C;Hu L;Tang Y;Zhang Q;Liang M;Hong J

文献摘要

参考文献

被引文献

相似文献

肝细胞癌复发率高、预后差,迫切需要寻找新的预测肝癌侵袭和预后的标志物。在这项研究中,我们研究了一个新的癌基因家族的两个成员Musashi1(MSI1)和Musashi2(MSI2)在40例正常肝组织、149例肝癌组织及其邻近非肿瘤组织中的表达模式。我们观察到MSI1和MSI2在肝细胞癌组织中显著上调。MSI1和MSI2的高表达分别在37.6%(56/149)和49.0%(73/149)的肝细胞癌组织中检测到,而在癌旁非肿瘤组织和正常肝组织中均未检测到。然而,只有MSI2的高表达与预后不良相关。此外,MSI2上调与代表高侵袭性肝细胞癌的临床病理参数相关。进一步研究表明,MSI2可能通过诱导上皮-间充质转化(EMT)增强肝癌的侵袭性。MSI2基因敲除显著降低了肝癌细胞的侵袭力,改变了EMT标志物的表达模式。此外,149例肝细胞癌组织标本的免疫组织化学分析进一步证实了这种相关性。综上所述,我们的研究结果表明,MSI2与EMT相关,有可能成为一种新的预测肝癌预后和侵袭性的生物标志物,帮助指导肝癌术后患者的诊断和治疗。
The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6% (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely detected in adjacent non-tumourous tissues and were never detected in normal hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated with poor prognosis. In addition, MSI2 up-regulation correlated with clinicopathological parameters representative of highly invasive HCC. Further study indicated that MSI2 might enhance invasion of HCC by inducing epithelial–mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the invasion of HCC cells and changed the expression pattern of EMT markers. Moreover, immunohistochemistry assays of 149 HCC tissue specimens further confirmed this correlation. Taken together, the results of our study demonstrated that MSI2 correlates with EMT and has the potential to be a new predictive biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of post-operative HCC patients.
DOI: 10.4161/cbt.10.10.14010
发表时间: 2010-11-15
影响因子: 3.6
作者:
Griner, Lori N.;Reuther, Gary W.
通讯作者: Reuther, Gary W.
DOI: 10.1016/s0896-6273(00)80277-9
发表时间: 1996-07-01
期刊: NEURON
影响因子: 16.2
作者:
Spana, EP;Doe, CQ
通讯作者: Doe, CQ
DOI: 10.1073/pnas.232087499
发表时间: 2002-11-12
影响因子: 11.1
作者:
Sakakibara, S;Nakamura, Y;Okano, H
通讯作者: Okano, H
DOI: 10.3233/dma-2011-0812
发表时间: 2010-01-01
期刊: CANCER BIOMARKERS
影响因子: 3.1
作者:
Liu, Dong-Cai;Yang, Zhu-Lin;Jiang, Song
通讯作者: Jiang, Song
DOI: 10.1056/nejmoa0708857
发表时间: 2008-07-24
影响因子: 158.5
作者:
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者: Bruix, Jordi