Exploring TBL1XR1 and NCOR1 Expression in B-cell Lymphoma Subtypes: Interaction With DNA Damage Repair Genes

Abstract

Background/aim: B-cell lymphomas are characterized by diverse genetic anomalies affecting B-cell differentiation. To expand targeted therapies, an in-depth grasp of the molecular dynamics in the germinal center (GC) is vital. Transducin β-like 1 X-linked receptor 1 (TBL1XR1) and nuclear receptor corepressor 1 (NCOR1) are instrumental within the GC, modulating myriad oncogenic pathways. Their prognostic roles in various cancers are established, yet their precise impact on B-cell lymphoma is elusive.

Materials and methods: Digital RNA quantification (Nanostring) of previously curated 188 B-cell lymphoma specimens across four subtypes, follicular lymphoma (FL), diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), primary testicular lymphoma (PTL), and plasmablastic lymphoma (PBL), was reanalyzed with focus on TBL1XR1 and NCOR1 expression, juxtaposing them with 730 ontogenically linked genes.

Results: Notably, TBL1XR1 expression was significantly elevated in the PTL- ABC-subtype versus DLBCL-NOS- ABC-subtype (p<0.001), with no marked disparity in GCB-subtypes between them. The median TBL1XR1 expression was remarkably diminished in FL, yet, intriguingly, GCB-subtypes of DLBCL-NOS exhibited significantly enhanced expression compared to FL (p=0.001). In contrast, NCOR1's expression trajectory was consistent across DLBCL-NOS, PTL, and PBL. A strong inverse correlation between TBL1XR1 and NCOR1 was observed in PBL (p=0.001). Importantly, TBL1XR1's pronounced association with several DNA Damage repair (DDR) genes was noted suggesting influence on DNA repair. TBL1XR1-DDR gene signature was further validated employing a public data set of DLBCL-NOS.

Conclusion: Our exploratory findings unravel the expression patterns of TBL1XR1/NCOR1 in B-cell lymphoma variants. The TBL1XR1-DDR genes connection offers insights into potential DNA repair roles, paving avenues for innovative therapies in B-cell lymphomas.

Keywords: NCOR1; RNA expression; TBL1XR1; diffuse large B-cell lymphoma; follicular lymphoma; plasmablastic lymphoma; primary testicular lymphoma.