Open Access
ARTICLE
Co-expression of CCR7 and H3K9me3 identifies aggressive B-cell lymphoma with bone marrow infiltration and poor prognosis
Jiawen Chen1,#, Zelin Liu1,#, Keke Huang1, Jinlan Li1, Yajie Zhang1, Dandan Chen1, Yanjie Ruan2, Ying Pan1, Furun An1, Yang Wan1,*, Jiyu Wang1,3,*, Qianshan Tao1,*
1 Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
2 Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
3 Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan, China
* Corresponding Author: Yang Wan. Email: 
; Jiyu Wang. Email: 
; Qianshan Tao.
Email: 
or 
European Cytokine Network https://doi.org/10.32604/ecn.2026.077875
Received 18 December 2025; Accepted 05 March 2026; Published online 01 April 2026
Abstract
Objectives: B-cell lymphoma exhibits significant clinical heterogeneity, necessitating improved biomarkers for risk stratification. C-C chemokine receptor 7 (CCR7) and trimethylation of histone H3 lysine 9 (H3K9me3) are implicated in cellular senescence and tumor invasion. While the clinical significance of their co-expression in lymphomagenesis remains unclear. This study aims to define the expression profiles of CCR7 and H3K9me3 in B-cell lymphoma, explore their correlation with aggressive clinical indicators, and evaluate their combined prognostic value. Methods: The expression of CCR7 and H3K9me3 in tumor tissues from B-cell lymphoma patients was analyzed by immunohistochemical (IHC) double-staining. The mechanistic association between the two was verified by co-immunoprecipitation assays and Western blot (WB) experiments detecting changes in cellular H3K9me3 levels following CCR7 ligand stimulation. The association between co-expression and patient clinical parameters, tumor burden, and progression-free survival (PFS) was evaluated through correlation analysis, Kaplan-Meier survival curves, and Cox regression analysis. Results: H3K9me3 expression was predominantly nuclear, whereas CCR7 was expressed on the cell membrane. Both markers were significantly upregulated in aggressive lymphomas and positively correlated with LDH, β2-microglobulin, and neutrophil percentage. An interaction between CCR7 and H3K9me3 could be demonstrated in that CCR7 ligand stimulation resulted in an upregulation of H3K9me3 expression. Enhanced H3K9me3 expression was associated with bone marrow infiltration. High expression of CCR7 was associated with poorer progression-free survival (PFS), whereas high expression of both CCR7 and H3K9me3 identified patients with the worst prognosis. Univariate and multivariate Cox regression analysis indicated that the combined expression was a potential prognostic biomarker for B-cell lymphoma. Conclusion: Co-elevated CCR7 and H3K9me3 expression defines a high-risk B-cell lymphoma subgroup with high tumor burden, bone marrow infiltration, and poor prognosis, highlighting their potential as biomarkers for risk stratification and candidate therapeutic targeting.
Keywords
B-cell lymphoma; C-C chemokine receptor 7; trimethylation of histone H3 lysine 9; immunohistochemistry double staining; bone marrow infiltration; prognosis
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