TROP2 expression in the gastroenteropancreatic neuroendocrine tumors: An analysis of 179 patients.

4148 Background: Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein that exhibits overexpression in various gastrointestinal (GI) malignancies, including colorectal, gastric, pancreatic, and esophageal cancers. This overexpression has been correlated with increased tumor aggressiveness, enhanced proliferation, and unfavorable prognostic outcomes. TROP2 serves as a predictive and prognostic biomarker in several GI cancers, guiding targeted therapy and correlating with overall survival. However, there exists a notable absence of dedicated studies investigating TROP2 expression specifically in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) highlighting an unmet need. This report presents the first and most extensive prospective study examining TROP2 overexpression in GEP-NETs. Methods: We utilized transcriptomic and clinical data derived from the National Cancer Institute's (NCI) GEP-NET project, which originates from a prospective study approved protocol (NCT05237934). For data analysis, we implemented the RNA-sequencing pipeline developed by the NCI Cancer Center Bioinformatics Resource ( https://github.com/skchronicles/RNA-seek.git ) along with STAR version 2.7.11b for aligning sequencing reads to the hg38 reference genome. To accommodate the variations introduced by different library preparation methodologies (including polyA, total RNA, FFPE, and access), we employed the "RemoveBatchEffect" function from the Limma package, while also accounting for disease-specific variations. Results: Our analysis included a total of 179 GEP-NET samples, comprised of 106 small bowel neuroendocrine tumors (NETs) and 73 pancreatic neuroendocrine tumors (pNETs). There were 54 females and 52 males in the small bowel cohort, and 37 females and 36 males in the pancreatic cohort. Notably, TROP2 expression was observed in 50% of pancreatic samples and 30% of small bowel NET samples. Furthermore, TROP2 expression appeared to correlate with decreased survival in pNETs (p=0.022), whereas its expression in small bowel NETs may suggest improved patient outcomes, although this latter correlation did not achieve statistical significance (p=0.37). Further analyses are pending study completion and will be presented later. Conclusions: This study highlights the critical role of TROP2 overexpression in GEP-NETs and its importance for patient prognosis. TROP2 overexpression correlates with decreased survival outcomes in pNETs relative to small bowel NETs. Additionally, the identification of TROP2 as a prognostic and predictive biomarker presents opportunities for future research focused on therapeutic targeting. Additional studies may be needed for further validation as we finalize the current research.