Expression of Raptor and Rictor and their relationships with angiogenesis in colorectal cancer

Fei-Fei Wen, Xin-Yan Li, Yang-Yang Li, Shuang He, Xiao-Yang Xu, Yuan-Hang Liu, Liu Liu,  Shu-Hua Wu

Abstract:

Mammalian target of rapamycin (mTOR) has two subtypes, i.e., mTORC1 and mTORC2, which contain the Raptor and Rictor core molecules, respectively. The effect of Raptor and Rictor on hypoxia inducible factor (HIF)-1α, HIF-2α, and vascular endothelial growth factor (VEGF) in colorectal cancer (CRC) is unclear. In this work, we investigated the correlations among Raptor, Rictor, HIF-1α, HIF-2α, and VEGF expression in CRC. We subsequently analyzed the clinicopathological features of patients. Immunohistochemistry, western blot, and RT-PCR analyses were performed 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 was used to label microvascular density (MVD), which was found to be higher in patients with positive Raptor or Rictor than in those with negative Raptor or Rictor. The positive rates of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in CRC were significantly higher than in normal colorectal mucosa. Raptor expression was positively correlated with HIF-1α and VEGF but not with HIF-2α expression. By contrast, Rictor expression was positively correlated with HIF-2α and VEGF but not with HIF-1α expression. Survival analysis further indicated that Raptor, Rictor, HIF-1α, HIF-2α, VEGF and lymph node metastasis were independent prognostic factors in CRC. To conclude, Raptor and Rictor expression was related to the initiation and development of CRC and angiogenesis in different ways. The combined detection of Raptor and Rictor is important for patients with colorectal carcinoma in prognosis and optimal therapy.