GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345774/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345774GEOGSEfalseLongitudinal Analysis of Matched Patient Biospecimens Reveals Neural Reprogramming of Cancer-Associated Fibroblasts Following Chemotherapy in Pancreatic CancerPancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer, is a deadly disease with a complex tumor microenvironment (TME). How chemotherapy alters the TME, and whether these changes drive chemoresistance, is poorly understood. We examined matched pre- and post-treatment tissue specimens and found near-universal enrichment of axonal guidance genes in cancer-associated fibroblasts (CAFs) after treatment. These CAFs were enriched near sites of perineural invasion, coinciding with regions of increased tumor cell proliferation, and were enriched in tumor areas distant from nerves after chemotherapy. Metastatic recurrence lesions had the highest prevalence of these CAFs versus primary tumors and untreated metastases. These CAFs showed elevated non-canonical Wnt mediators and axonal guidance genes, which complemented matching cognate binding partners in tumor epithelial cells, suggesting a role in tumor-stroma crosstalk. Additionally, in vitro studies revealed enrichment of axonal guidance genes in patient-derived CAF lines upon exposure to chemotherapy or tumor cells. Altogether, our findings implicate fibroblast-derived axonal-guidance genes in promoting PDAC invasion and point to a promising target for this disease.2026/09/10GSE345774GSM10016231GSM10016230GSM10016235GSM10016234GSM10016233GSM10016232GSM10016228GSM10016227GSM10016237GSM10016236GSM1001622924676345774Homo sapiens