The clinical significance and oncogenic function of LRRFIP1 in pancreatic cancer

Abstract

Abstract Purpose Pancreatic cancer is a lethal malignancy with a grim prognosis. Previous studies have proven that Leucine Rich Repeat of Flightless-1 Interacting Protein 1 (LRRFIP1) plays a pivotal role in cell biological processes, while its clinical significance and function in pancreatic cancer remain to be elucidated. Hence, we aimed to explore the roles and mechanisms of LRRFIP1 in pancreatic cancer. Methods The expression of LRRFIP1 in pancreatic cancer tissues and its clinical significance for pancreatic cancer were analyzed by immunohistochemistry assay and bioinformatic analysis. The influences of LRRFIP1 on the proliferation and migration of pancreatic cancer cells were assessed in vitro. The underlying mechanisms of LRRFIP1 in pancreatic cancer progression were explored using gene set enrichment analysis (GSEA) and molecular experiments. Results The results showed that LRRFIP1 expression was significantly upregulated in pancreatic cancer tissues compared to the normal tissues, and such upregulation was associated with poor prognosis of patients with pancreatic cancer. GSEA revealed that LRRFIP1 upregulation was significantly associated with various cancer-associated signaling pathways, including PI3K/AKT signaling pathway and Wnt pathway. Furthermore, LRRFIP1 was found to be associated with the infiltration of various immune cells. Functionally, LRRFIP1 silencing suppressed cell proliferation somewhat and inhibited migration substantially. Further molecular experiments indicated that LRRFIP1 silencing inactivated the AKT/GSK-3β/β-catenin signaling axis. Conclusion Taken together, LRRFIP1 is associated with tumorigenesis, immune cell infiltration, and prognosis in pancreatic cancer, which suggests that LRRFIP1 may be a potential biomarker and therapeutic target for pancreatic cancer.

Keywords

• Pancreatic cancer
• Prognosis
• LRRFIP1
• AKT
• GSK-3β
• β-catenin