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.).
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Carrier Proteins/metabolism , Colorectal Neoplasms/metabolism , Drug Resistance, Multiple/genetics , Membrane Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Autophagy , Beclin-1 , Carrier Proteins/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease Progression , Female , Humans , Immunohistochemistry , Lymphatic Metastasis/genetics , Lymphatic Metastasis/pathology , Male , Membrane Proteins/genetics , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Middle Aged , Prognosis , Rapamycin-Insensitive Companion of mTOR Protein , Regulatory-Associated Protein of mTOR , Survival Rate , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
Purpose To investigate the expression of Beclin1, LC3 and mTOR in colorectal cancer ( CRC) and their significance. Methods Immunohistochemistry, Western blot and real-time PCR were employed to detect the expression of Beclin1, LC3 and mTOR in CRC. Results The positive expression rate of Beclin1, LC3 and mTOR in 242 cases of CRC was 90. 50%, 87. 19% and 46. 28%, respectively, which were higher than that in adjacent tissues ( P0. 05). The expres-sion of LC3 was positively correlated with Beclin1 and negatively correlated with mTOR in colorectal cancer (rs =0. 593, P0. 05). Kaplan-Meier survival analysis re-vealed that the five-year survival rate of patients without nodal metastasis, positive expression of Beclin1, LC3 and negative expression of mTOR was higher than those with nodal metastasis, negative expression of Beclin1 and LC3, and positive expression of mTOR. Cox survival analysis results revealed that LC3, mTOR and lymphnode metastasis were independent prognostic factors. The results of IHC, real-time PCR and Western blot in fresh CRC tissues indicated that the expression of Beclin1, LC3 and mTOR in colorectal cancer was significantly higher than that in adjacent tissues (P<0. 05). Conclusions The aberrant expression of Beclin1, LC3 and mTOR may be associated with the development and progression of colorectal cancer. The simultaneous detection of Beclin1, LC3 and mTOR genes in colorectal cancer may be helpful for the evaluation of the progressive degree and the judgment of prognosis.
