The Clinical And Mechanism Study Of Adrenal Pheochromocytoma Angiogenesis

OBJECTIVE: Pheochromocytoma is an adrenal medullary tumor characterized by a(pseudo)hypoxic environment.Increased angiogenesis not only causes intraoperative bleeding,but also promotes malignant progression of the tumor.This study intends to(1)investigate proteins related to angiogenesis in adrenal pheochromocytoma;(2)explore the molecular mechanism of angiogenesis in adrenal pheochromocytoma,providing a theoretical basis for tumor treatment.METHODS:(1)The quantitative proteomics were used to explore pheochromocytoma angiogenesis-related proteins,verified by quantitative real-time PCR and immunohistochemistry.(2)Cellular function was detected in mouse pheochromocytoma cells after induction of pseudo-hypoxia and addition of epinephrine.RESULTS:(1)Among the proteins screened by quantitative proteomics,COX4I2 was verified to be increased gradually with microvessel density with increasing severity,and PLAT was shown to be decreased with microvessel density in pheochromocytoma,by quantitative real-time PCR and immunohistochemistry.(2)The pheochromocytoma data in the TCGA database showed that COX4I2 was significantly associated with VEGFA and HIF2 A.In mouse pheochromocytoma cell,HIF2 A and COX4I2 level were significantly increased by pseudo-hypoxia and epinephrine,while COX4I2 level were decreased after adding epinephrine receptor inhibitor.Induction of pseudo-hypoxia promoted increased tube formation of human umbilical vein endothelial cells and increased epinephrine level.CONCLUSION:(1)COX4I2 and PLAT were highly correlated with blood supply in pheochromocytoma which may contribute to angiogenesis in pheochromocytoma,which could be used as biomarkers to better indicate tumor angiogenesis,or targets to regress tumor angiogenesis as treatment.(2)Epinephrine/HIF2α/COX4I2 may participated in angiogenesis of pheochromocytoma,which deserves further study to verify the mechanism of pheochromocytoma angiogenesis.