Abstract
The diagnosis of primary pancreatic neuroendocrine tumors (pNETs) presents significant challenges, and metastatic pancreatic neuroendocrine tumors are associated with high mortality. Understanding the characteristics of these tumors, particularly the key molecules involved in metastasis, is essential. To address this, we utilized mRNA expression data from human pNET and metastatic pancreatic tumor tissues available in the GEO database and integrated this data with bioinformatics analyses. And then we collected clinical primary tumor and liver metastasis samples from patients with pNETs, we conducted a comprehensive analysis of circular RNAs (circRNAs) to identify key circRNAs associated with the onset and metastasis of pNETs. We found that in pNET development and metastasis, 11 genes and 14 circRNAs were notably upregulated, while 25 genes and 35 circRNAs were significantly downregulated, compared to nearby non-cancerous tissue. Our analysis of differentially expressed RNA and circRNA genes revealed that tumor cell adhesion and integrin activation, regulated by genes like PIEZO1, IFT74, SKAP1, GPX1, F7, VTN, and OMG, are strongly linked to pNET metastasis. We found that SKAP1 levels are positively associated with tumor progression in pNET patients. Overall, our research indicates that the SKAP1-mediated pathway is crucial in pNET development and metastasis.