Secretogranin II serves as a potential prognostic biomarker and correlates with the immune microenvironment in pancreatic neuroendocrine tumors

Background: Pancreatic neuroendocrine tumors (pNETs) present diagnostic and therapeutic challenges because of their rarity and heterogeneity. This study aimed to identify key genes involved in the development of pNETs and potentially effective prognostic biomarkers. Methods: We analyzed three datasets from the Gene Expression Omnibus, which included 135 pNET and 13 normal tissues, to identify secretogranin II (SCG2) as a key gene in pNETs. Enrichment analysis revealed that SCG2 expression was negatively correlated with inflammatory responses and interferon signaling. Immune infiltration analysis showed that high SCG2 expression was associated with lower Stromal, Immune, and ESTIMATE scores and a shift in immune cell composition, including reduced γδ T cells and M1 macrophages, and increased M2 macrophages. Potential therapeutic molecules, including telomerase inhibitors and caspase activators, were identified using the Connectivity Map. In our clinical validation of 130 patients with pNETs from The Fourth Hospital of Hebei Medical University, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) confirmed higher SCG2 expression in pNET tissues. Results: SCG2 was significantly upregulated in pNETs. High SCG2 expression was associated with significantly lower Stromal, Immune, and ESTIMATE Score. Significant reductions in γδ T cells and macrophages M1, and a significant increase in macrophages M2 were observed, accompanied by a significant decline in various immune chemokines in the high SCG2 expression group. The expression of SCG2 in pNETs was significantly higher, as verified by qRT-PCR and IHC in clinical cohorts. Furthermore, high SCG2 expression was associated with shorter overall survival [hazard ratio (HR) =1.68; 95% confidence interval (CI): 1.432–7.408; P=0.005] and disease-free survival (HR =4.997; 95% CI: 1.288–19.386; P=0.02), establishing it as an independent prognostic factor for pNETs. Conclusions: These findings indicate that SCG2 is a potential prognostic marker and therapeutic target for pNETs. It may be involved in disease progression by modulating the tumor immune microenvironment, suggesting a possible role in prognostic evaluation and clinical management.