胃癌组织Skp2表达的意义及其与P27、PTEN表达的关系

背景与目的:S期激酶相关蛋白2(S-phaseKinase-associatedProtein2,Skp2)促进泛素介导的细胞周期素依赖激酶抑制剂P27蛋白降解,是细胞G1-S期转化所必需。研究发现Skp2过表达参与细胞转化和肿瘤的形成。本研究旨在探讨人胃癌Skp2表达的意义及Skp2与P27和PTEN表达的关系。方法:采用免疫组化法检测胃癌组织及配对癌旁胃粘膜138例、配对淋巴结转移癌组织102例、非典型增生30例、肠上皮化生30例、慢性浅表性胃炎10例和正常胃粘膜5例Skp2表达及138例胃癌P27和PTEN的表达。结果:Skp2的标记率(%)在肠化(12.68±0.86)及癌旁胃粘膜(19.32±1.22)均明显高于慢性浅表性胃炎(0.53±0.13)及正常胃粘膜(0.47±0.19)(P<0.001),后两者无显著性差异(P﹥0.05);非典型增生(16.74±0.82)明显高于肠化(P<0.001);原发胃癌(31.34±2.17)明显高于非典型增生及癌旁胃粘膜(P<0.001);淋巴结转移胃癌组织(39.76±2.00)明显高于原发胃癌(P=0.037)。胃癌Skp2标记率与分化程度(rs=0.315,P=0.000)、脉管内瘤栓(rs=0.303,P=0.000)及淋巴结转移(rs=0.254,P=0.000)呈正相关。胃癌Skp2表达与靶蛋白P27表达(rs=-0.451,P=0.000)和肿瘤抑制蛋白PTEN(rs=-0.480,P=0.000)表达呈负相关;胃癌PTEN表达与P27表达呈正相关(rs=0.642,P=0.000)。结论:胃癌Skp2蛋白过表达与P27蛋白降解及PTEN蛋白低表达有关,提示Skp2蛋白过表达可能是胃癌发生和发展的一个重要原因。

Correlation of Skp2 expression in gastric carcinoma to expression of P27 and PTEN

BACKGROUND & OBJECTIVE: S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of cyclin-dependent kinase inhibitor P27. Its overexpression has been involved in cell transformation and tumorigenesis. This study was to investigate the significance of Skp2 expression in human gastric carcinoma and its correlation to expression of both P27 and PTEN. METHODS: The expression of Skp2 in 138 specimens of gastric cancer and their paired adjacent mucosa, 102 specimens of paired metastatic lymph nodes, 30 specimens of dysplasia, 30 specimens of intestinal metaplasia, 10 specimens of chronic superficial gastritis, and 5 specimens of normal gastric mucosa, and the expression of P27 and PTEN in 138 specimens of gastric cancer were detected by immunohistochemistry. RESULTS: Skp2 labeling frequency was significantly higher in intestinal metaplasia (12.68+/-0.86)%] and adjacent mucosa (19.32+/-1.22)%] than in chronic superficial gastritis (0.53+/-0.13)%] and normal gastric mucosa (0.47+/-0.19)%] (P<0.001), but there was no difference between chronic superficial gastritis and normal gastric mucosa (P>0.05); Skp2 labeling frequency was significantly higher in dysplasia (16.74+/-0.82)%] than in intestinal metaplasia (P<0.001), significantly higher in primary gastric carcinoma (31.34+/-2.17)%] than in dysplasia and adjacent mucosa (P<0.001), and significantly higher in metastatic lymph node (39.76+/-2.00)%] than in primary gastric carcinoma (P=0.037). Skp2 labeling frequency in gastric carcinoma was positively correlated with differentiation grade (rs=0.315, P<0.001), vessel invasion (rs=0.303, P<0.001), and lymph node metastasis (rs=0.254, P=0.001). Skp2 expression was negatively correlated with both P27 expression (rs=-0.451, P<0.001) and PTEN expression (rs=-0.480, P<0.001) in gastric carcinoma. P27 expression was positively correlated with PTEN expression in gastric carcinoma (rs=0.642, P<0.001). CONCLUSION: Skp2 overexpression, which may lead to degradation of P27 and low expression of PTEN, may be a very important reason in carcinogenesis and progression of gastric carcinoma.