p-mTOR与HIF-1α在结直肠癌组织中的表达及其临床意义

The expression of p-mTOR and HIF-1α in colorectal cancer tissues and its clinical implication

目的:研究磷酸化雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、缺氧诱导因子(hypoxia-inducible factor,HIF)-1α在结直肠癌组织中的表达,探讨其与结直肠癌临床病理特征及预后的关系。方法:收集2007年6月至2013年12月在济南军区总医院普外科行手术切除并经病理证实的结直肠癌组织及癌旁正常黏膜组织标本,免疫组织化学方法检测p-mTOR、HIF-1α在63例结直肠癌组织、27例转移淋巴结组织、12例转移癌组织中的表达,以癌旁正常黏膜组织作对照,χ~2检验分析p-mTOR、HIF-1α的表达与临床病理特征的关系。p-mTOR和HIF-1α表达的相关性采用Spearman相关分析,Kaplan-Meier检验进行p-mTOR、HIF-1α的生存期分析。结果:在结直肠癌组织中,p-mTOR(50.80%vs 6.35%,χ~2=30.489,P<0.01)、HIF-1α(65.08%vs 9.52%,χ~2=47.323,P<0.01)的阳性率均显著高于正常结直肠组织;p-mTOR、HIF-1α表达与肿瘤的分期及远处转移及淋巴结转移相关,而且p-mTOR表达与HIF-1α表达呈正相关(r=0.345,P<0.01);p-mTOR阳性患者的无疾病进展生存期及总生存期均显著短于p-mTOR阴性患者(χ~2分别为4.584、4.557,均P<0.05)。结论:p-mTOR及HIF-1α在结直肠癌组织及转移癌组织中表达升高,其表达可以作为结直肠癌临床病理分期及预后的重要指标。

Objective: To examine the expression of phosphorylated mammalian target of rapamycin( p-mTOR) and hypoxia-inducible factor-1α( HIF-1α) in colorectal cancers and investigate its association with pathological features and prognosis. Methods: Surgical resected colorectal carcinoma and adjacent normal tissues were collected from patients with colorectal cancer enrolled into Jinan Military General Hospital from June,2007 to December,2013. Immunohistochemistry was performed to detect the expression of p-mTOR and HIF-1α in 63 cases of colorectal carcinoma tissues,27 cases of metastatic lymph node tissues,and 12 cases of metastasized carcinoma tissues,with adjacent normal tissues as controls. χ~2 test was used to analyze the relationship between p-mTOR and HIF-1α expression and clinical pathological features.Spearman correlation analysis was performed to analyze the association between p-mTOR and HIF-1α expression; KaplanMeier test was used for survival analysis related to p-mTOR and HIF-1α expression. Results: In colorectal carcinoma tissues,the positive rate of p-mTOR( 50. 80% vs 6. 35%,P < 0. 01) and HIF-1α( 65. 08% vs 9. 52%,P < 0. 01) was significantly higher than that of normal colorectal tissues. The expression of HIF-1α was correlated with distant metastasis,TNM stage and lymph node metastasis( P < 0. 05),and there was a positive correlation between p-mTOR and HIF-1α expression( r = 0. 345,P < 0. 01). Furthermore,the disease-free survival time and overall survival time of p-mTOR positive patients were significantly shorter than that of p-mTOR negative patients( P < 0. 05). Conclusion: The expression of pmTOR and HIF-1α are increased in colorectal cancer tissues,which are informative markers for clinical pathological staging and are useful prognosis factors.