Expression of stearoyl coenzyme A desaturase in neuronal cells facilitates pancreatic cancer progression

Background: Pancreatic adenocarcinoma (PDAC) is a fatal malignant tumor that focuses on men and the elderly (40–85 years) and is aggressive. Its surgical resection rate is only 10%-44%, and the rate of local recurrence in the retroperitoneum 1 year after surgery is as high as about 60%. The main reason for local recurrence in the majority of patients is that PDAC is perineural invasion (PNI) and the cancer cells infiltrate and grow along the peripancreatic nerve bundles. The identification of biomarkers associated with the diagnosis of PDAC may help to improve the current difficulty in early diagnosis of pancreatic cancer and guide clinical treatment. We constructed a co culture model of Schwann cells and PDCA cells, and determined that Stearoyl Coenzyme A Desaturase (SCD) is a key gene driving the progress of PDAC. Methods: Single-cell data files for PDAC were analyzed to compare cellular composition and subpopulation-specific gene expression between control (n = 4) and pancreatic cancer (n = 6). Among 36,277 cells, we obtained a total of 16 subpopulations, including a Neurons subpopulation, by UMAP analysis. Further screening by Mendelian randomization analysis yielded three pairs of genes corresponding to eQTL-positive outcome causally, the corresponding genes were, in order: the three genes COL18A1, RASSF4, and SCD. Among them, SCD was significantly positively correlated with Macrophages.M0 and so on, and significantly negatively correlated with Mast cells resting and so on. In this study, we further co-cultured Schwann cells and PDAC cells in a co-culture model, and knocked down the SCD of neuronal cells using CRISPR-Cas9 technology to detect the proliferation and migration ability of PDAC cells. Results: Three genes (COL18A1, RASSF4, SCD) showed significant correlation with PDAC. The identified SCD genes were positively correlated with the development of PDAC. We further demonstrated experimentally that SCD was overexpressed in PDAC tissues and that knockdown of SCD in neuronal cells reduced the proliferation and migration of PDAC cells. Conclusion: This study demonstrated that the upregulation of SCD expression level in neuronal cells is associated with the development of PDAC, and SCD may be a potential target for PDAC therapy.