The tumor suppressor role of Src homology phosphotyrosine phosphatase 2 in hepatocellular carcinoma
The tumor suppressor role of Src homology phosphotyrosine phosphatase 2 in hepatocellular carcinoma
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DOI：
10.1007/s00432-011-1143-5
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发表时间：
2012-04-01
影响因子：
3.6
通讯作者：
Wei, Lixin
中科院分区：
文献类型：
--
作者：
Jiang, Chengying;Hu, Fangke;Wei, Lixin
人类基因 PTPN11 编码 Src 同源磷酸酪氨酸磷酸酶 2 (Shp2) 的非受体蛋白酪氨酸磷酸酶，之前已被很好地解释为多种恶性肿瘤中的原癌基因。然而，Shp2 的肿瘤抑制作用也有报道。本研究旨在探讨Shp2表达及其在肝细胞癌(HCC)中的作用及其相关临床表现。构建了333对HCC及自配癌旁非肿瘤组织的组织芯片，采用免疫组化法检测Shp2的表达。结果还通过 31 个自配对新鲜 HCC 标本的蛋白质印迹和定量 PCR 得到证实。分析了 Shp2 表达与 25 种临床病理特征的关联。进行总生存分析和多因素分析，肿瘤组织（T）中Shp2表达较癌旁非肿瘤组织（NT）显着降低，阳性率分别为66.1%和96.7%。我们通过Shp2表达减少的变量（Delta Shp2）组合T和NT Shp2免疫反应性，并将病例分为2组：T < NT和T a 千分之一NT。生存分析显示低Shp2表达和T<NT组均与较短的总生存期显着相关。多变量分析显示Delta Shp2是一个独立的预后标志物(P = 0.033; HR: 0.527; 95% CI: 0.293-0.950)。Shp2是一种抑癌基因，Shp2表达的降低是HCC新的预后标志物。 Shp2的致癌作用具有组织特异性，人类基因PTPN11的治疗靶点应重新考虑。
The human gene PTPN11, which encodes the non-receptor protein tyrosine phosphatase of Src homology phosphotyrosine phosphatase 2 (Shp2), has been previously well interpreted as a proto-oncogene in a variety of malignancies. However, the tumor suppressor role of Shp2 has also been reported. The present study was conducted to investigate the role of Shp2 expression and its associated clinical manifestations in hepatocellular carcinoma (HCC).A tissue microarray of 333 pairs of HCC and self-matched adjacent non-tumor tissues was constructed, and the expression of Shp2 was determined by immunohistochemistry. The results were also conformed by Western blotting and quantitative PCR of 31 self-paired fresh HCC specimens. The associations of Shp2 expression with 25 clinicopathologic features were analyzed. Overall survival analysis and multivariate analysis were performed.Significantly decreased Shp2 expression in tumor tissues (T) compared with adjacent non-tumor tissues (NT) could be detected, and the positive rate was 66.1 and 96.7%, respectively. We combined the T and NT Shp2 immunoreactivity by a variable of the decrease in Shp2 expression (Delta Shp2) and divided cases into 2 groups: T < NT and T a parts per thousand yen NT. Survival analysis showed both low Shp2 expression and T < NT group were significantly associated with short overall survival. Multivariate analysis showed Delta Shp2 was an independent prognostic marker (P = 0.033; HR: 0.527; 95% CI: 0.293-0.950).Shp2 is a tumor suppressor, and the decrease in Shp2 expression was a new prognostic marker in HCC. The oncogenic role of Shp2 was tissue specific, and the therapeutic target of human gene PTPN11 should be reconsidered.