Raptor、Rictor与结直肠癌血管生成的相关性及其临床意义

Relationships of Raptor and Rictor expression with angiogenesis in colorectal cancer and their clinical significance

目的检测Raptor、Rictor与血管生成相关因子HIF-1α、HIF-2α以及VEGF在结直肠癌中的表达,探讨Raptor、Rictor与结直肠癌血管生成的相关性及其临床意义。方法采用免疫组化、Western blot、RT-PCR法检测120例结直肠癌组织及60例正常结直肠黏膜组织中Raptor、Rictor及HIF-1α、HIF-2α、VEGF的表达及其差异;CD34标记微血管密度(microvascular density,MVD);分析各指标间的相关性以及与结直肠癌临床病理特征的关系。结果 Raptor、Rictor、HIF-1α、HIF-2α和VEGF蛋白在结直肠癌中的阳性率均明显高于正常结直肠黏膜组织(P<0.05)。Raptor、Rictor在中、低分化结直肠癌中的表达高于高分化结直肠癌(P<0.05),同时在淋巴结转移组的表达高于无淋巴结转移组(P<0.05);HIF-1α、HIF-2α和VEGF在淋巴结转移组的表达高于无淋巴结转移组(P<0.05);Raptor、Rictor阳性的结直肠癌组织中MVD明显高于Raptor、Rictor阴性的结直肠癌组织(P<0.05);Raptor与HIF-1α、VEGF在结直肠癌中表达呈正相关(P<0.01),Rictor与HIF-2α、VEGF表达呈正相关(P<0.01),Raptor与Rictor在结直肠癌中表达呈负相关(P<0.01)。结论 m TOR核心分子Raptor、Rictor与结直肠癌的发生、发展及血管生成密切相关,两者以不同途径协同促进结直肠癌的血管生成。

Purpose To detect the expression of Raptor, Rictor, angiogenesis-related factors HIF-1α, HIF-2α and VEGF and to investigate their relationship and significance in colorectal cancer （CRC）. Methods Immunohistochemistry, Western blot and RT-PCR were employed to detect the expression of Raptor, Rictor, HIF-1α, HIF-2α and VEGF in 120 cases of CRC and 60 cases of normal colorectal mucosa. CD34 labeled microvascular density （MVD） was also observed. The correlations between Raptor, Rictor, HIF-1α, HIF-2α, VEGF expression and the patients＇ clinicopathological features were analyzed. Results The positive rates of Raptor, Rictor, HIF-1α, HIF-2α and VEGF in CRC were significantly higher than those in normal colorectal mueosa （ P 〈 0. 05 ）. Raptor and Rictor expression was correlated with the degree of tumor differentiation and lymph node metastasis, respectively. The expression of HIF-1α, HIF-2α and VEGF was higher in patients with lymph node metastasis than those in patients without lymph node metastasis （P 〈 0. 05 ）. The MVD was higher in patients with Raptor or Rictor positive than that in patients with Raptor or Rictor negative （ P 〈 0. 05 ）. The expression of Raptor was positively correlated with HIF-1α and VEGF （P 〈 0. 01 ） , the expression of Rictor was positively correlated with HIF-2α and VEGF （ P 〈 0. 01 ）, but the expression of Raptor was negatively correlated with Rictor （ P 〈0. 01 ）. Conclusion The expression of mTOR core mole- cules Raptor and Rictor is related to the initiation and development of colorectal cancer and angiogenesis, and they promote angiogenesis in colorectal cancer by different ways.