Pathology Department, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
J Cancer Res Clin Oncol. 2012 Apr;138(4):637-46. doi: 10.1007/s00432-011-1143-5. Epub 2012 Jan 7.
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 (ΔShp2) and divided cases into 2 groups: T < NT and T ≥ NT. Survival analysis showed both low Shp2 expression and T < NT group were significantly associated with short overall survival. Multivariate analysis showed ΔShp2 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.
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，先前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 表达及其相关临床表现在肝细胞癌（HCC）中的作用。
构建了 333 对 HCC 和自我匹配的相邻非肿瘤组织的组织微阵列，并通过免疫组织化学检测 Shp2 的表达。还通过 31 对自我配对的新鲜 HCC 标本的 Western blot 和定量 PCR 对结果进行了确认。分析了 Shp2 表达与 25 种临床病理特征的关联。进行了总生存分析和多变量分析。
可以检测到肿瘤组织（T）中 Shp2 表达明显低于相邻非肿瘤组织（NT），阳性率分别为 66.1%和 96.7%。我们通过 Shp2 表达降低的变量（ΔShp2）将 T 和 NT 的 Shp2 免疫反应性结合起来，并将病例分为 2 组：T < NT 和 T ≥ NT。生存分析表明，低 Shp2 表达和 T < NT 组均与总生存期短显著相关。多变量分析表明，ΔShp2 是独立的预后标志物（P = 0.033；HR：0.527；95%CI：0.293-0.950）。
Shp2 是一种肿瘤抑制基因，Shp2 表达降低是 HCC 的新预后标志物。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。
