摘要

Background: Esophageal Squamous Cell Carcinoma (ESCC) has a poor prognosis. The application of targeted drugs in ESCC is limited. Aim: To investigate the correlation between vascular endothelial growth factor (VEGF) and clock genes PER1, PER2, determine the daily rhythm of VEGF in ESCC patients. Methods: PER1, PER2 and VEGF were evaluated by Quantitative RT-PCR, western blot and Immunohistochemistry (IHC). The concentration of VEGF was evaluated by enzyme linked immunosorbent assay (ELISA). 36 blood samples and 36 urine samples were collected from patients with ESCC, and 36 blood samples were collected from normal people at four time points in a day. Results: Decreased level PER1 and PER2 and increased level of VEGF were observed in ESCC cancer tissues. The levels of PER1 and PER2 were negatively, while the level of VEGF was positively associated with factors of lymph node metastasis and clinical staging (P < 0.001). A significant negative correlation was found between PER1, PER2 expression and VEGF expression in cancer specimen and the blood of ESCC patients. The concentrations of VEGF differed in the blood and urine of ESCC patients and in normal person blood at different times in a day (03:00, 09:00, 15:00, 21:00). In particularly, the expression level of VEGF exhibited daily rhythmic variations, reaching the highest at 15:00 and lowest at 21:00. Conclusion: Down-regulation of PER1, PER2 and increased expression of VEGF might promote tumor progression in ESCC. The optimized time selection for VEGF administration for ESCC patients is at 15: 00, when VEGF expression reaches peak.