Transcriptomic profiling reveals complement activation in chronic pancreatitis adjacent to pancreatic ductal adenocarcinoma

Short abstract: Chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) frequently coexist, yet distinguishing inflammatory changes secondary to malignancy from primary pancreatitis remains challenging. Here, we present an integrated multi-omics analysis of spatially distinct pancreatic tissue compartments obtained from a single patient undergoing pancreaticoduodenectomy for PDAC, combining histopathology, transcriptomics, immunofluorescence, and meta-transcriptomic microbial profiling. Morphological assessment identified tumor tissue, adjacent chronic pancreatitis, and normal pancreas. Transcriptomic profiling of macro-dissected samples revealed differential gene expression and enrichment of the classical complement pathway in the CP compartment, which was qualitatively supported by immunofluorescent detection of C1q and C3 along the ductal epithelium. Meta-transcriptomic analysis detected a limited number of bacterial taxa and no viral RNA; these findings were interpreted conservatively given the constraints of low-biomass tissue profiling and the single-patient design. Although causal inference and generalizability are limited by the single-patient design, this study demonstrates the feasibility of integrating pathology with transcriptomic and microbial analyses to generate hypothesis-generating, multi-omics framework for exploring inflammatory-malignant interactions in pancreatic disease.