FLNB overexpression promotes tumor progression and associates with immune suppression, evasion and stemness in pancreatic cancer

Pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies that enhance or recruit antitumor immune cells into the tumor microenvironment (TME) remain promising strategies for PC treatment. Consequently, a deeper understanding of the molecular mechanisms involved in PC immune suppression is critical for developing immune-based therapies to improve survival rates. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify Filamin B (FLNB) correlated with the infiltration of CD8 T cells and tumor-associated macrophages (TAMs). The clinical significance and potential biological function of FLNB were evaluated using bioinformatic analysis. The oncogenic role of FLNB in PC was determined using and studies. We further analyzed possible associations between FLNB expression and tumor immunity using CIBERSORT, single sample gene set enrichment analysis, and ESTIMATE algorithms. We found FLNB was overexpressed in PC tissues and was correlated with poorer overall survival, tumor recurrence, larger tumor size, and higher histologic grade. Moreover, FLNB overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. Functional enrichment analysis identified the role of FLNB in the regulation of cell cycle, focal adhesion, vascular formation, and immune regulation. Knockdown of FLNB expression inhibited cancer cell proliferation and migration in-vitro and suppressed tumor growth in-vivo. Furthermore, FLNB overexpression caused high infiltration of Treg cells, Th2 cells, and TAMs, but reduced infiltration of CD8 T cells and Th1/Th2. Collectively, our findings suggest FLNB promotes PC progression and may be a novel biomarker for PC.