High expression of RHOF is an effective diagnostic marker and a potential prognostic indicator for primary mediastinal large B-cell lymphoma.

Due to the overlap of histological and molecular features of primary mediastinal large B-cell lymphoma (PMBL) with other lymphomas and its low incidence, the diagnosis and prognostic assessment of PMBL pose certain challenges. This study included 51 PMBL and 375 diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) from the GEO database and 65 PMBL and 117 DLBCL-NOS from a single center. At the transcriptional and protein levels, RHOF expression in PMBL was significantly higher than in DLBCL-NOS (P < 0.001). ROC curve analysis suggested that high RHOF expression had a high discriminative diagnostic ability for PMBL and DLBCL-NOS (transcriptional level, AUC = 0.913-0.940; protein level, AUC = 0.878). Comparing RHOF with commonly used PMBL diagnostic markers CD23, CD30, and PD-L1, it was found that high RHOF expression is a more useful diagnostic marker for PMBL (AUC (RHOF) = 0.878 > AUC (CD23) = 0.818 > AUC (CD30) = 0.756 > AUC (PD-L1) = 0.590). The diagnostic model based on CD23, CD30, and RHOF exhibits higher sensitivity for the diagnosis of PMBL than any of the individual markers mentioned above. Concerning prognosis, high RHOF transcriptional expression was significantly associated with poorer overall survival (OS) in PMBL (P = 0.00037), while high RHOF protein expression was significantly associated with poorer OS and progression-free survival (PFS) in PMBL (P = 0.034; P = 0.034). This study indicates that high RHOF expression in PMBL is closely associated with the diagnosis, prognosis, and clinical pathological features of the disease. High RHOF expression demonstrates a superior diagnostic ability in distinguishing PMBL from DLBCL-NOS compared to existing markers. Furthermore, research on RHOF expression in PMBL holds promise for providing new targets and insights for prognosis assessment and treatment of PMBL.