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. 2025 Jun 3;15(1):19391.
doi: 10.1038/s41598-025-04349-x.

Differential expression of proliferation and immune response genes between children and adults influences survival of diffuse large B cell lymphoma

Tamara Mangiaterra  1 , Ruth Alonso-Alonso  2 , Andrés Rabinovich  1 , David Herman  3 , Marcela De Dios Soler  4 , Laura Galluzzo  5 , Marcela Soria  6 , Sandra Colli  7 , Elena De Matteo  1   7 , Socorro María Rodriguez Pinilla  2 , Paola Chabay  8
Affiliations

Differential expression of proliferation and immune response genes between children and adults influences survival of diffuse large B cell lymphoma

Tamara Mangiaterra et al. Sci Rep. .

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a neoplasm affecting adults and children, with different clinical behaviors between age groups. To shed light on those differences, gene expression profiling was evaluated in 48 formalin-fixed paraffin-embedded biopsies of patients with DLBCL. Sixteen differentially expressed genes in pediatric DLBCL compared to adults were demonstrated, involving lymphocyte differentiation, oncogenic signaling and chemotaxis. Pathway analysis confirmed the enrichment in proliferation-related pathways. In addition, the increased presence of NKCD56dim cells in pediatric patients suggests a cytotoxic immune response in this group, perhaps explaining their better outcome. Exclusion of Epstein Barr virus (EBV) + DLBCL, NOS, showed, in pediatric cases, additional downregulated genes associated with immune regulators and checkpoint genes. This suggested EBV infection may have on the modulation of immune response in pediatric lymphomas. Survival analysis showed associations between genes such as MYC, NT5E and CD34, and event-free survival in pediatric patients. Furthermore, higher expression of MYC in children displayed higher risk of death or relapse, while lower expression of NT5E and CD34 was associated with lower risk. This study identifies distinct immune response and proliferation gene expression patterns in pediatric DLBCL compared to adults, and the interaction with tumor microenvironment, with potential implications for disease pathogenesis.

Keywords: Children; DLBCL; EBV; Gene expression; Pathways; Survival.

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Conflict of interest statement

Declarations. Consent to participate: All the patients or patients’ guardians gave informed consent for the study. Ethics statement: Institutional guidelines regarding human experimentation were followed, in accordance with the Helsinki Declaration of 1975. The Ricardo Gutierrez Children’s Hospital Ethics Committee approved the study. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Volcano blots plot for each group analyzed. (a) The upregulated (red)/downregulated (blue) genes for Pediatrics vs. Adults DLCBL, NOS cases, including EBV + cases. (b) The upregulated (red)/downregulated (blue) genes for Pediatrics vs. Adults DLCBL cases excluding EBV + cases.
Fig. 2
Fig. 2
Box plot for each group analyzed. (a) NKCD56dim cells types between Pediatric vs. Adults DLCBL, NOS total cases. (b) NKCD56dim cells types between Pediatric vs. Adults DLCBL excluding EBV + cases. (c) Mast cells types between Pediatric vs. Adults DLCBL excluding EBV + cases. (d) Dendritic cells types between Pediatric vs. Adults DLCBL excluding EBV + cases.
Fig. 3
Fig. 3
Diagram KEGG pathway enrichment analysis for DLCBL, NOS total cases. (a) Pathway for significantly upregulated genes. (b) Pathway for significantly downregulated genes.
Fig. 4
Fig. 4
Diagram KEGG pathway enrichment analysis for DLCBL, NOS excluding EBV + cases. (a) Pathway for significantly upregulated genes. (b) Pathway for significantly downregulated genes.
Fig. 5
Fig. 5
Event-free survival in pediatric patients with DLBCL, NOS. (a) Event-free survival for MYC gene. (b) Event-free survival for NT5E gene. (c) Event-free survival for CD34 gene.
See this image and copyright information in PMC

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