Transcriptomic profiling reveals autophagy-associated programs and prognostic biomarkers in anoikis-resistant pancreatic cancer cells

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastatic progression and poor clinical outcomes. During metastatic dissemination, detached tumor cells must overcome anoikis, a form of apoptosis induced by loss of extracellular matrix attachment. Although anoikis resistance is considered a critical prerequisite for metastasis, the adaptive mechanisms supporting detached survival in pancreatic cancer remain incompletely understood. In this study, anoikis-resistant (AR) pancreatic cancer cell models were established through repeated long-term suspension culture using Capan-1 and PSN-1 cells. Transcriptomic profiling was performed to identify conserved molecular programs associated with anoikis resistance in PDAC. Gene set variation analysis (GSVA) demonstrated consistent transcriptomic enrichment of autophagy-associated and suppression of cell cycle-related pathways in both AR models. Differential expression and integrative pathway analyses further identified several core genes associated with autophagy regulation and cytokine signaling. Survival analysis revealed that elevated expression of UBC and ATG14 was associated with poor prognosis in pancreatic cancer patients. Our findings suggest that suspension-selected pancreatic cancer cells undergo coordinated stress-adaptive transcriptional remodeling characterized by enriched autophagy- and ubiquitin-associated transcriptional programs.