Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine
Introduction: Pancreatic cancer remains highly resistant to genomic and molecular targeted therapies. Recent pan-cancer genome analyses have shown a correlation between chromosome copy number amplification and driver gene density, highlighting chromosomal amplification as a key factor in cancer progression. Aim: This study aims to identify novel driver genes in pancreatic cancer, elucidate tumorigenesis mechanisms, and develop targeted therapies. Methods: 1. Bioinformatic analyses of TCGA datasets identified candidate driver genes. 2. Immunohistochemical staining of pancreatic cancer specimens validated gene expression levels and its clinical correlations. 3. Genetically engineered cell lines with target gene modifications were analyzed for proliferation, invasion, and metastasis, along with associated signal pathways. 4. A drug repositioning approach was employed to identify potential therapeutic compounds. Results: SPRR1B was identified as a novel driver gene candidate. High SPRR1B expression correlated with significantly worse survival. Immunohistochemical analysis revealed a significantly higher number of SPRR1B-positive cells in tumor tissues compared to normal pancreatic tissues (p=0.002). Pathway analysis linked SPRR1B to the Epithelial-Mesenchymal Transition (EMT) pathway. In Panc-1 and PK-59 cell lines, SPRR1B knockdown reduced invasiveness in wound healing assays. Furthermore, drug repositioning identified tiracizine, prochlorperazine maleate, and mepenzolate bromide as potential therapeutic agents. Conclusion: SPRR1B may serve as a novel therapeutic target for pancreatic cancer. Further comprehensive studies are needed.