Multi-Omic and Spatial Profiling Identifies an Epithelial DKK1 Associated with Microenvironmental Remodeling in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic datasets and subsequently validated bulk differential expression and network analyses with machine learning-based prioritization in an independent combined cohort (TCGA-PAAD plus GSE62452). Single-cell mapping was used to assess cell-type specificity, positioning candidates along inferCNV- and pseudotime-defined malignant continua. In Visium sections, a DKK1-associated program score quantified intratumoral spatial heterogeneit

SUBMITTER: Xu J 

PROVIDER: S-EPMC12939099 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature