Supplementary Material for: Prognostic Role of Circular RNAs in Mantle Cell Lymphoma: A Competing Endogenous RNA Network Analysis

Objective: This study evaluated the prognostic role of circular RNAs (circRNAs) in individuals diagnosed with mantle cell lymphoma (MCL), using the framework of the competing endogenous RNA (ceRNA) network model. Methods: Differentially expressed circRNAs were identified from the GSE159808 dataset, and differentially expressed messenger RNAs (mRNAs) were extracted from GSE32018. Corresponding microRNAs (miRNAs) were retrieved to construct a ceRNA regulatory network relevant to MCL. Functional enrichment analysis and survival analysis were performed on 35 mRNAs incorporated in the ceRNA network to identify transcripts associated with survival outcomes in MCL. A prognostically relevant ceRNA subnetwork was then constructed based on these results. Results: Thirteen circRNAs (9 upregulated, 4 downregulated) and 457 differentially expressed mRNAs were identified. The initial ceRNA network included 11 circRNAs, 40 miRNAs, and 35 mRNAs. Gene Ontology analysis indicated enrichment in pathways related to dentin-containing tooth development, the plasma membrane signaling receptor complex, and growth factor receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated significant involvement in the B-cell receptor signaling pathway, Fc gamma receptor-mediated phagocytosis, and the Wnt signaling pathway. Survival analysis identified six mRNAs significantly associated with overall survival in individuals with MCL. These results were used to derive a refined prognostic ceRNA network consisting of 6 mRNAs, 7 miRNAs, and 6 circRNAs. Conclusion: CircRNAs may regulate MCL prognosis by modulating miRNA–mRNA interactions within the ceRNA network. These findings suggest a regulatory mechanism by which circRNAs contribute to molecular pathways influencing disease progression and survival in MCL.