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Published on: September 30, 2016
Expression of Raptor and Rictor and their relationships with angiogenesis in colorectal cancer
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.
Insights
Mammalian target of rapamycin (mTOR) pathway components Raptor and Rictor are linked to colorectal cancer (CRC) growth and angiogenesis. Their expression correlates with hypoxia-inducible factors and VEGF, impacting patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Mammalian target of rapamycin (mTOR) signaling, through mTORC1 (Raptor) and mTORC2 (Rictor), plays a role in cancer.
- The specific roles of Raptor and Rictor in colorectal cancer (CRC) concerning hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) remain unclear.
Purpose of the Study:
- To investigate the correlations between Raptor, Rictor, HIF-1α, HIF-2α, and VEGF expression in colorectal cancer.
- To analyze the relationship between these molecular markers and clinicopathological features, including microvascular density (MVD) and patient prognosis.
Main Methods:
- Immunohistochemistry, western blot, and RT-PCR were used to assess the expression of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in 120 CRC tissues and 60 normal colorectal mucosa samples.
- CD34 staining was performed to quantify microvascular density (MVD).
Main Results:
- Positive rates of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF were significantly higher in CRC tissues compared to normal tissues.
- Raptor expression correlated positively with HIF-1α and VEGF, while Rictor expression correlated positively with HIF-2α and VEGF.
- Higher MVD was observed in patients with positive Raptor or Rictor expression. Raptor, Rictor, HIFs, VEGF, and lymph node metastasis were identified as independent prognostic factors.
Conclusions:
- Raptor and Rictor expression are associated with colorectal cancer initiation, development, and angiogenesis through distinct mechanisms.
- Combined assessment of Raptor and Rictor expression may aid in predicting prognosis and guiding optimal therapy for colorectal cancer patients.
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