Effect of Glucose Variability on Pancreatic Cancer Through Regulation of COL6A1

BACKGROUND: Pancreatic cancer (PC), a devastating cancer worldwide, remains dismal prognosis due to its clinical elusiveness, especially in relation to diabetes mellitus (DM). The study aims to investigate the effect of glucose variability on COL6A1 in PC cancer cells and the prognostic potential of COL6A1 for PC patient associated with DM. METHODS: After PC cancer cell lines of AsPC-1 and BxPC-3 were treated with hyperglycemia and hypoglycemia, Giemsa staining and Transwell chamber were performed to assay plate clone formation, migration and invasion. Expressions of COL6A1 of PC cancer cell lines under different extracellular glucose levels were detected by qRT-PCR and Western blotting. The level of COL6A1 expression in PC patients with/without DM was further observed with immunohistochemistry. The prognostic impact of COL6A1 on PC patients with DM was assessed by Kaplan–Meier survival curve analysis. RESULTS: Hyperglycemia promoted proliferation, migration and invasion of PC cancer cells compared with hypoglycemia. Glucose variability could regulate expression of COL6A1 in PC cancer cells, both Col6a1 mRNA and COL6A1 protein upregulated in cancer cells cultured with hyperglycemic than that with hypoglycemic. The level of COL6A1 expression was higher in PC patients with DM than that without DM. Besides, COL6A1 was significantly associated with the clinical prognosis of PC patients with DM, higher COL6A1 leading to lower overall survival (OS). CONCLUSION: Glucose variability had effect on PC cancer cells through regulation of COL6A1. Accordingly, COL6A1 was associated with poorer prognosis in PC patients with DM.