A novel lipid droplet-related prognostic signature reveals CIDEC as a key biomarker for pancreatic adenocarcinoma.

PURPOSE: Reprogramming of lipid metabolism is acknowledged as a key characteristic of cancer. This research aimed to examine the potential of lipid droplet-associated genes (LDRGs) in forecasting patient outcomes and the effectiveness of immunotherapy in pancreatic adenocarcinoma (PAAD). METHODS: A predictive signature was developed through LASSO Cox regression analysis. Survival predictions were assessed via Kaplan-Meier survival analysis, along with univariate and multivariate Cox regression analyses. Associations between LDRGs and tumor-immune infiltration, as well as immune checkpoints, were examined using Spearman's analysis. The pivotal gene CIDEC within the LDRGs was pinpointed, and a CIDEC-associated competing endogenous RNA (ceRNA) regulatory network was established employing comprehensive bioinformatics analysis. The pro-tumor phenotype of CIDEC was explored in PAAD cell lines through molecular experiments. RESULTS: A signature model related to LDRGs for determining the prognosis of PAAD was constructed, based on which patients were classified into two risk groups. A nomogram accompanied by calibration curves was constructed, which proved a robust predictive value. Additional investigations revealed that these prognostic LDRGs are significantly associated with levels of immune infiltration and the expression of immune checkpoints. Through ceRNA network analysis, a regulatory axis involving LINC00365, hsa-miR-32-5p, hsa-miR-363-3p, and CIDEC was identified in PAAD. Experimental evidence indicates that elevated CIDEC expression markedly enhances proliferation, migration, and invasion capabilities in PAAD cell lines while simultaneously suppressing apoptosis. Conversely, reduced CIDEC levels produce the opposite effects. CONCLUSION: In conclusion, our novel prognostic signature model has promising applications in PAAD patients. Within this framework, CIDEC may serve as a valuable candidate biomarker and a potential target for therapeutic intervention, thereby providing a basis for future research. The LINC00365/hsa-miR-32-5p/hsa-miR-363-3p/CIDEC regulatory axis may be involved in the progression of PAAD.