Multi-Omics Profiling Reveals the Interplay Between Genomic Instability and Microenvironmental Remodeling in Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PNETs) represent a biologically heterogeneous group of neoplasms shaped by both intrinsic genomic alterations and dynamic interactions with the tumor microenvironment (TME). Conventional analytical approaches offered limited insight into these complex mechanisms. However, the emergence of multi-omics technologies including genomics, transcriptomics, proteomics, and spatial single-cell platforms dramatically expanded our understanding of tumor evolution, immune-stromal crosstalk, and phenotypic plasticity. In this review, we discuss the recent integrated omics findings to highlight co-evolutionary dynamics between tumor cells and the TME, uncover novel biomarkers, and explore therapeutic implications. We further propose that multi-omics analysis offers not only a descriptive snapshot of tumor composition but also a mechanistic framework for precision oncology. This paradigm enables more accurate patient stratification and the identification of actionable vulnerabilities that may guide targeted therapeutic strategies in PNETs.