ABSTRACT
PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.
Subject(s)
Pancreatic Neoplasms , Humans , Biomarkers , Glycogen Phosphorylase, Brain Form/genetics , Glycogen Phosphorylase, Brain Form/metabolism , MAP Kinase Signaling System/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Prognosis , Signal Transduction/geneticsABSTRACT
Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Quercetin/analogs & derivatives , Humans , Early Detection of Cancer , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Molecular Docking Simulation , Pancreas , Gene Expression Profiling , Apoptosis/genetics , Prognosis , Gene Expression Regulation, Neoplastic , Membrane Proteins , Receptors, Lysophosphatidic AcidABSTRACT
BACKGROUND: Biliary ascariasis is rare but remains the most common parasitic infection in remote areas and in people with poor medical conditions. Here, we reported a case of biliary ascariasis in order to raise awareness of possible parasitic infections. CASE SUMMARY: A 68-year-old female was admitted to the emergency room of the Affiliated Hospital of Guizhou Medical University on 28 September 2017, with chief complaint of pain in the right upper abdomen. Ultrasonography of the abdomen showed that the upper segment of the common bile duct was slightly dilated with parallel tubular structures, indicative of biliary ascariasis. Endoscopic retrograde cholangiopancreatography was performed under general anesthesia on 29 September 2017, and an adult Ascaris lumbricoides worm was observed. After the worm was removed from the bile duct, the patient's pain immediately subsided. The patient was successfully cured, without any complications. CONCLUSION: This report emphasizes the need for physicians to consider biliary ascariasis as a possible cause when treating cases of biliary colic.
