IL27 expression and IL27RA-dependent cellular responses are associated with biochemical recurrence and...

Biochemical recurrence remains a clinically heterogeneous event in prostate cancer, yet the immune signals associated with relapse-prone tumors are not fully defined. This study investigated IL-27 and its receptor IL27RA as a potential immune-epithelial ligand-receptor axis linking microenvironmental inflammation, recurrence, and immune escape.

Transcriptomic and clinical datasets from TCGA and GEO were analyzed to assess IL-27 expression, biochemical recurrence-free survival, clinicopathological associations, immune infiltration, pathway activity, single-cell distribution, mutation features, and druggable-target patterns. Experimental validation was performed in RWPE-1 prostate epithelial cells and PC-3 prostate cancer cells using immunofluorescence staining, recombinant IL-27 stimulation, IL27RA knockdown, CCK-8 assays, and qRT-PCR.

Higher IL27 expression was observed in prostate cancer and was associated with recurrence, higher Gleason score, and shorter biochemical recurrence-free survival; the association with recurrence persisted after adjustment for the clinicopathological variables included in the Cox model.

These findings identify IL27 expression as a recurrence-associated molecular feature in retrospective prostate cancer datasets and provide proof-of-concept evidence for an IL27RA-dependent response to IL-27 in PC-3 cells.