Establishment of M2 macrophage-related prognostic signature in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by significant heterogeneity and a poor prognosis. M2 macrophages (M2) play a crucial role in the microenvironment of PDAC, yet their exact functional significance remains poorly understood. This study sought to explore the potential communication and clinical implications of M2 in PDAC. The differentiation pathway of M2 and their interaction with malignant PDAC cells were analyzed using single-cell RNA sequencing (scRNA-seq). Additionally, a prognostic signature related to M2 marker genes was constructed and analyzed using bulk RNA sequencing. Three distinct differentiation states of M2 were characterized, each exhibiting unique transcription factor expression profiles and signaling pathway activations. Potential intercellular communication between M2, PDAC malignant cells, and fibroblasts was initially observed at the level of computer analysis. The prognostic model was identified through the LASSO algorithm. Patients stratified by risk level displayed significant variations in prognostic indicators such as signaling pathway activity, gene mutation frequency, immune cell infiltration, and drug sensitivity. These findings are of course preliminary, and future in vitro/in vivo experiments will be needed to knock out these signature genes or ligand-receptor pairs of genes in macrophages to validate their role in macrophage development.