Prognostic significance and pathogenesis of RFC3 gene expression in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype in adults. Dysregulation of replication factor C subunit 3 (RFC3) gene expression were associated with disease progression and poor prognosis in various cancer types. However, its significance in DLBCL remains largely unexplored. This study aimed to characterize RFC3 expression patterns, clinical relevance, functional mechanisms, and potential therapeutic implications in DLBCL.

Multi-omics analyses were performed using data extracted from the Gene Expression Omnibus (GEO) project (GSE181063, GSE10846, GSE32918, GSE31312, GSE32018, and GSE12453) and The Cancer Genome Atlas (TCGA). RFC3 expression was validated via immunohistochemistry (IHC) in DLBCL samples. Survival analysis was conducted using the Kaplan-Meier method. The chi-square test was used to assess the association between RFC3 expression and clinical characteristics of DLBCL. Gene Set Enrichment Analysis (GSEA) was employed to identify tumor signaling pathways associated with RFC3. Immune infiltration was evaluated using the Immuno-Oncology Biological Research (IOBR) package. Drug sensitivity analysis was performed using the oncoPredict package, and immunotherapy response was assessed via the IMvigor210 dataset. Pan-cancer analysis was conducted using the easyTCGA and TCGAplot packages available on the R software.

RFC3 expression was significantly upregulated in DLBCL. High RFC3 expression was closely associated with poor prognosis, adverse clinical features, and adverse tumor microenvironment characteristics in DLBCL patients. Furthermore, multiple tumor proliferation and cancer-related signaling pathways were significantly enriched in the high RFC3 expression group. The pan-cancer analysis also revealed elevated RFC3 expression across several tumor types. Elevated RFC3 expression was strongly correlated with worse tumor prognosis.

RFC3 may serve as a novel prognostic biomarker and a potential therapeutic target for DLBCL. Further investigations into the mechanisms underlying RFC3 dysregulation may provide important insights for future diagnostic and therapeutic strategies.