Identification of the driving mechanisms associated with aggressive transformation and prognosis in follicular lymphomas

Abstract

Abstract Follicular lymphoma (FL) is the most frequently common indolent subtype of non-Hodgkin’s lymphoma (NHL), with a generally favorable prognosis. Recent studies have elucidated a subset of patients undergoing histological transformations (HTs) into transformed follicular lymphoma (tFL) and diffuse large B-cell lymphoma (DLBCL) aggressive morphology, leading to a poorer prognosis. Investigating the mechanisms of oncogenic transformation further could be helpful to find potential prognostic biomolecular markers that could be used to develop new treatment strategies or combination strategies. In this study, we conducted integrative bioinformatics analyses of the GEO, DAVID, STRING, GeneMANIA, TRRUST, and DGIdb database to determine which hub genes contributed to aggressive HTs of FL. The results show that HTs-related 462 and 503 differential genes contained between tFL and FL as well as between DLBCL and FL, respectively. Further functional enrichment analysis of these differential genes showed that the common significant enrichment in cell division, immune response, mitotic spindle organization, chromosome segregation of biological processes (BPs), extracellular space, extracellular region, and external side of the plasma membrane of cellular components (CCs), protein binding, microtubule-binding, heparin-binding, extracellular matrix structural constituent, and integrin binding of molecular functions (MFs), and cytokine-cytokine receptor interaction, chemokine signaling pathway, and viral protein interaction with cytokine and cytokine receptor signaling pathway of KEGG pathways. Subsequently, construct an overlapping PPI network to screen 10 hub genes (CCNB1, AURKA, RRM2, CDK1, BUB1B, CDC6, ASPM, TTK, TPX2, and NCAPG). We then analyzed the transcription factor regulation and drug regulatory networks. In summary, our study identified 3 oncogenic transformation molecules (CDK1, RRM2, and AURKA) as important biomarkers in the progression of FL. Their abnormal expression is closely associated with prognosis and sensitivity to standard therapy and can help us better understand the aggressive HTs of FL.