The effects of CYP24A1 on clinicopathological features and the prognosis of pancreatic ductal adenocarcinoma.

Abstract

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a type of exocrine pancreatic cancer that presents itself in the form of a highly malignant tumor. However, in the past few decades, with breakthroughs in the diagnosis and treatment of malignant tumors, there have yet to be satisfactory results for the diagnosis (early diagnosis) and treatment of PDAC. Therefore, the biological behavior of PDAC still requires more research to be understood. CYP24A1 is currently considered to be an essential part of vitamin D (VD) metabolism and increasingly reported to be associated with malignant tumors. Therefore, this study aims to explore the relationship between CYP24A1 and the clinicopathological features and prognosis of PDAC.MethodsSeventy-three surgical PDAC cases were collected and follow-ups were made. The expression of CYP24A1 was obtained by the immunohistochemistry and the tissue FAXS cytometry (TFC) system. The related quantitative indices included the percentage of positive cells (%) and the average staining intensity of the positive cells (in) in the cancer zone (C) and the adjacent non-cancer zone (ANC). The relationship between CYP24A1 and the clinicopathological parameters, as well as the prognosis of PDAC was then analyzed. Furthermore, Fluorescence quantitative PCR, Western-blot, siRNA, and phenotypic testing were implemented in the Pan-C1 PDAC cells.ResultsIn normal pancreatic tissue, CYP24A1 was approximately “zero-expressed” in the exocrine glands. In the C and ANC zones, the expression of CYP24A1 increased significantly. In cases with a higher C%, the proportion of lymph node metastasis was lower (P=0.071); In cases with a higher ANC% (P=0.026) and higher ANCin (P=0.079), the proportion of high differentiation was higher; in survival analysis, C%, Cin had a significant effect on survival and those with higher parameters had a lower risk of death. In the cell experiments, after CYP24A1 was silenced, the migration ability of PDAC cells did not change significantly and its proliferation (P=0.034) and invasion (P=0.002) ability decreased significantly.ConclusionsCYP24A1 has a significant effect on the development and prognosis of PDAC.