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[摘要]
目的:探讨结直肠癌组织中S6蛋白激酶 1(protein S6 kinase 1, S6K1)和真核翻译起始因子-4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1, 4EBP1)的表达情况及其与结直肠癌患者临床病理参数之间的关系。方法:收集济南军区总医院肿瘤科2007年1月至2009年12月收治的有完整临床病理资料、经手术切除的100例结直肠癌组织与40例正常癌旁结直肠黏膜组织、30例淋巴结转移灶组织、15例远处转移灶组织,用免疫组化方法检测上述组织中S6K1和4EBP1蛋白的表达,并分析其与患者临床病理参数之间的关系。结果:S6K1和4EBP1蛋白在正常结直肠黏膜组织中的阳性表达率分别为17.50%(7/40)和22.50%(9/40),而在结直肠癌组织中的阳性表达率分别为74.00%(74/100)和79.00%(79/100),S6K1和4EBP1蛋白在癌和正常结直肠黏膜组织中的阳性表达率间差异均有统计学意义(P<0.01);在结直肠癌组织中,S6K1蛋白的阳性表达与结直肠癌患者的临床分期(r=0.31,P<0.01)及组织分化程度(r=0.25,P<0.05)显著相关。4EBP1蛋白的阳性表达与结直肠癌患者的临床分期(r=0.27,P<0.01)及组织分化程度(r=0.22,P<0.05)显著相关。S6K1和4EBP1蛋白高表达患者无疾病进展时间(progression free survival, PFS)更短(P<0.05),但S6K1和4EBP1蛋白表达水平对患者的总生存期(overall survival, OS)无影响(P>0.05)。S6K1和4EBP1蛋白两者的阳性表达呈正相关(r=0.25,P<0.05)。结论:S6K1及4EBP1蛋白在结直肠癌形成过程中有互相促进作用,与结直肠癌的发生发展及预后相关,可作为较为理想的分子靶点和预后评估指标。
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[Abstract]
Objective:To investigate the expression of protein S6 kinase1(S6K1)and eukaryotic translation initiation factor 4E binding protein 1(4EBP1)in colorectal cancers and their relationship with clinicopathologic characteristics. Methods:The data of 100 patients diagnosed with colorectal cancer from January of 2007 to December of 2009 were collection from the General Hospital of Ji'nan Military Command of PLA. The specimens include 100 colorectal cancer tissues, 40 normal tissues of the incisional edges, 30 metastatic lymph nodes, and 15 distant metastasis cancer tissues. Immunohistochemical S-P method was used to examine the expression of S6K1 and 4EBP1 in these tissues. Results: The positive rates of S6K1 and 4EBP1 were 17.50% (7/40) and 22.50% (9/40) respectively in normal colorectal tissues, and they increased significantly to 74.00% (74/100) and 79.00% (79/100) in colorectal cancer tissues. The expression of 4EBP1 in colorectal cancer tissues was associated with its clinical stage and differentiation status (P<0.05). Patients with colorectal cancers expressing high levels of S6K1 and 4EBP1 had shorter progression free survival (PFS) (P<0.05), whereas S6K1 and 4EBP1 expression had no association with overall survival (OS) (P>0.05). Further analysis revealed that there was a direct correlation between the levels of S6K1 and 4EBP1 in colorectal cancer tissues (r=0.246, P<0.05). Conclusion:The expression of S6K1 and 4EBP1 are related to the development, progress, and prognosis of colorectal cancer. Therefore, they are potential therapeutic targets and informative prognostic biomarkers.
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