High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies

Abstract

Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.

Keywords:

• RNA-sequencing
• ABC-DLBCL
• tumor evasion mediators
• MAPK10
• perturbagens

Acknowledgements

We thank Jairo Rodriguez and qgenomic for performing RNA-seq studies. We also wish to thank Javier Herruzo for his help with scrolls of DLBCL biopsies at the biobank in Cordoba, Spain. Figure 3(A) was created by BioRender.com. Finally, we want to thank to the Bioinformatics Unit of the IIS-FJD for help with GEO uploading.

Disclosure statement

All the authors declare no relevant conflicts of interest regarding the results reported in this paper and during its preparation.

Additional information

Funding

This work is supported by the Genomics Thailand project of Health Systems Research Institute; Junta de Andalucía of Spain; La Caixa Foundation.