ABSTRACT
Purpose To detect the expression of Raptor,Rictor,angiogenesis-related factors HIF-lα,HIF-2α and VEGF and to investigate their relationship and significance in eolorectal cancer (CRC).Methods Immunohistochemistry,Western blot and RT-PCR were employed to detect the expression of Raptor,Rictor,HIF-lα,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-2c,VEGF expression and the patients' clinicopathological features were analyzed.Results The positive rates of Raptor,Rictor,HIF-1c,HIF-2α and VEGF in CRC were significantly higher than those in normal colorectal mucosa (P ＜ 0.05).Raptor and Rictor expression was correlated with the degree of tumor diffcrentiation and lymph node metastasis,respectively.The expression of HIF-1α,HIF2α 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-2o and VEGF (P ＜ 0.01),but the expression of Raptor was negatively correlated with Rictor (P＜0.01).Conclusion The expression of mTOR core molecules 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.
ABSTRACT
UNLABELLED: This study aims to evaluate the relationship between the expressions of autophagy-related genes Raptor, Rictor, and Beclin1 and the expression of multidrug resistance (MDR) gene in colorectal cancer (CRC) patients. Immunohistochemistry and real-time polymerase chain reaction were used to detect the protein and messenger RNA expressions of mammalian target of rapamycin (mTOR), Raptor, Rictor, Beclin1, light chain 3 (LC3), and MDR-1 in 279 CRC specimens. Patients were followed up annually by telephone or at an outpatient clinic. Results revealed that the protein and messenger RNA expressions of Beclin1, LC3, mTOR, Raptor, Rictor, and MDR-1 in CRC are significantly higher than in adjacent tissues. LC3 expression in poorly differentiated CRC is higher than that in well-differentiated CRC, and the expression of mTOR, Raptor, Rictor, and LC3 in lymph node metastasis is higher than that obtained in the absence of lymph node metastasis. The expression of LC3 is positively correlated with those of Beclin1 and Rictor and negatively correlated with Raptor and mTOR in CRC. The expression of Raptor is negatively correlated with Rictor. The expression of MDR-1 is positively correlated with those of Beclin1, LC3, and Rictor and negatively correlated with Raptor and mTOR. Kaplan-Meier analysis revealed that the 5-year survival rate of patients without lymph node metastasis; positive expression of Rictor, Beclin1, and LC3; and negative expression of Raptor and mTOR were higher than those with these characteristics. To conclude, the expressions of Beclin1, Raptor, and Rictor are related to the development and progression of colorectal carcinoma and MDR. ( CLINICAL TRIAL REGISTRATION NUMBER: 2014-009-01.).
