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hnRNPAB/Kap1共同高表达促进肝癌预后不良

[High expression of hnRNPAB/Kap1 together promote poor prognosis in HCC].

作者信息

Zhou Z J, Wang X Y, Xu X Y, Hu Z Q, Chen E B, Zhou S L, Wu W Z, Zhou J, Fan J, Dai Z

机构信息

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2017 Jun 20;25(6):452-457. doi: 10.3760/cma.j.issn.1007-3418.2017.06.012.

Abstract

To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student -test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% 59% , = 1.67, < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% 54%, = 1.66, = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone ( = 1.35 /1.28, = 0.001) or in combination with Kap1 ( =1.24 /1.27, < 0.05) were independent prognostic indicators for overall survival and time to recurrence. In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

摘要

为进一步了解异质性核糖核蛋白AB(hnRNP AB)的相互作用蛋白谱,并探讨其在肝细胞癌(HCC)中的临床意义。我们进行了质谱分析以揭示KRAB相关蛋白1(Kap1)和hnRNPAB的特异性肽段,并通过免疫沉淀和蛋白质印迹法验证它们之间的相互作用。在组织芯片中通过免疫组织化学染色检测hnRNPAB/Kap1蛋白的表达。分类数据采用卡方检验或Fisher精确检验进行分析;组间计数数据采用Student检验或Wilcocon符号秩检验进行比较;累积复发率和生存率采用Kaplan-Meier方法评估,差异采用对数秩检验进行评估。我们确定Kap1是HCCLM3细胞和HepG2细胞中hnRNPAB的分子伴侣。我们发现Kap1高表达患者的5年生存率显著低于Kap1低表达组患者(36%对59%,z = 1.67,P < 0.001)。同样,Kap1高表达的HCC患者5年预后最差,累积复发率高于Kap1低表达患者(72%对54%,z = 1.66,P = 0.

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