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DLC-1是肝细胞癌中的一个独立预后标志物和潜在治疗靶点。

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer.

作者信息

Song L J, Liu Q, Meng X R, Li Sh L, Wang L X, Fan Q X, Xuan X Y

机构信息

Department of Oncology, the first affiliated hospital of Zhengzhou University, Henan, 450000, China.

Department of Neurosurgery, the fifth affiliated hospital of Zhengzhou University, Henan, 450000, China.

出版信息

Diagn Pathol. 2016 Feb 4;11:19. doi: 10.1186/s13000-016-0470-x.

DOI:10.1186/s13000-016-0470-x
PMID:26846339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4743322/
Abstract

BACKGROUND

The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood.

METHODS

With the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis.

RESULTS

DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability.

CONCLUSION

DLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC.

摘要

背景

由于肝细胞癌(HCC)患者在疾病早期就会发生侵袭和转移,其5年生存率很低。生物标志物可能有助于预测侵袭和转移的早期发生。越来越多的证据表明,肝癌缺失基因1(DLC1)在众多实体癌和血液系统癌症中可能被视为一种转移抑制基因。然而,其预后作用以及调节和协调这些活动的机制仍知之甚少。

方法

采用免疫组织化学方法,对80例肝癌组织及癌旁非癌组织中DLC-1以及Rho A、ROCK2、埃兹蛋白的表达进行了检测。还研究了它们的表达与肝癌临床病理特征之间的相关性及其相互关系。此外,通过Cox回归和Kaplan-Meier分析评估肿瘤组织中DLC1表达的预后价值。

结果

肝癌组织中DLC1表达明显低于癌旁非癌组织,且DLC-1表达与肿瘤分化、TNM分期及淋巴结转移呈负相关。此外,发现DLC-1表达与在肝癌组织中高表达的Rho A、ROCK2和埃兹蛋白呈负相关。Kaplan-Meier分析显示,与DLC1低表达的肝癌患者相比,DLC1高表达的患者5年生存率显著更长。多因素Cox比例风险分析显示,DLC1是影响总生存概率的独立因素。

结论

DLC1在肝癌进展尤其是侵袭和转移过程中可作为一种肿瘤抑制基因。DLC1可能通过调节Rho A、ROCK2和埃兹蛋白的表达发挥作用。评估DLC-1的表达可能是肝癌患者良好的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/35f4847c71ea/13000_2016_470_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/bf3533113455/13000_2016_470_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/360c3eded242/13000_2016_470_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/4ea19745fbf4/13000_2016_470_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/901f7ad59a7f/13000_2016_470_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/35f4847c71ea/13000_2016_470_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/bf3533113455/13000_2016_470_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/360c3eded242/13000_2016_470_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/4ea19745fbf4/13000_2016_470_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/901f7ad59a7f/13000_2016_470_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5fb/4743322/35f4847c71ea/13000_2016_470_Fig5_HTML.jpg

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