FSTL1 contribute to aggressive clinical behavior in DLBCL may by activating the DIP2A/ICAM-1-mediated adhesion mechanism.

INTRODUCTION

Despite improved outcomes in diffuse large B-cell lymphoma (DLBCL) with rituximab-based therapy, cell adhesion-mediated drug resistance (CAM-DR) remains a key mechanism of treatment resistance. The role of follistatin-like protein 1 (FSTL1) in CAM-DR has not been fully elucidated.

METHODS

We conducted a retrospective analysis of newly diagnosed DLBCL patients treated with rituximab from 2019 to 2024, with special emphasis on FSTL1 expression and clinical features, and its underlying mechanism.

RESULTS

FSTL1 was detectable in 74.5 % of patients. Its expression was significantly elevated in DLBCL patients compared to controls (P < 0.05) and was further increased in the RR-DLBCL group (P = 0.045). FSTL1 patients exhibited more adverse clinical features, including higher incidence of extranodal involvement, more advanced stage, elevated LDH levels, and bulky masses (all p < 0.05). FSTL1 expression patients revealed a shorter overall survival (OS) (p = 0.024) and progression-free survival (PFS) (p = 0.034), with similar trend in high FSTL1 expression (P < 0.05). In vitro, increased exogenous of FSTL1 contributed to DLBCL cell proliferation, vitality, and decreased the antibody-dependent cellular cytotoxicity (ADCC) effect, whereas FSTL1 silencing reversed this trend (P < 0.05). Pathway enrichment analysis revealed an association between FSTL1 and CAM-DR. Mechanistic experiments revealed that FSTL1 may be derived from secretion by cancer-associated fibroblasts (CAFs), interacts with DIP2A on DLBCL cells and promotes ICAM-1 expression, thereby contributing to drug resistance in DLBCL.

CONCLUSION

Our findings indicate that elevated FSTL1 levels may contribute to advanced clinical characteristics and worse outcomes in DLBCL. FSTL1 contributes to drug resistance likely through DIP2a/ICAM-1-mediated adhesion mechanism.