CEP55, A Promising Prognostic Biomarker for Pancreatic Neuroendocrine Neoplasms, Promotes Tumor Progression Through Activation of PI3K/AKT/mTOR Pathway

ABSTRACT Pancreatic neuroendocrine neoplasms (pNENs) exhibit significant heterogeneity, and the effectiveness of traditional classification methods in predicting tumor biological behavior and patient prognosis is limited. This study aims to reveal potential biomarkers to predict the prognosis of pNENs and explore the underlying mechanisms. Four mRNA sequencing datasets of pNENs were included in the study. CEP55, TPX2, and BIRC2 were identified as overlapping DEGs and were significantly associated with the clinical characteristics and prognosis of pNENs. The nomogram, which incorporated independent prognostic risk factors such as CEP55 expression, tumor grade, and TNM stage, demonstrated higher predictive efficiency than traditional methods. We found that knockdown of CEP55 resulted in the inhibition of proliferation, migration, and invasion in pNENs cells, while a reverse trend was observed in CEP55‐overexpressing cells. Furthermore, CEP55 was found to enhance the PI3K/AKT/mTOR pathway in pNENs through its interaction with PI3K‐p110. Everolimus, an mTOR inhibitor, was shown to counteract the effects of CEP55 overexpression both in vivo and in vitro. In conclusion, CEP55 may enhance the proliferation, invasion, and migration of pNENs by activating the PI3K/AKT/mTOR pathway through its interaction with PI3K. It may serve as a valuable prognostic marker and a promising therapeutic target.