Expression of nuclear factor kappa B and its correlation with prognosis in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma_West China Medical Journal

Authors：

WANG Cui , HUANG Junhua ,  XU Caigang , YANG Wanxi , MA Yanfeng , TIAN Ying

Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

XU Caigang, Email: xucaigang@wchscu.cn

Keywords：

Epstein-Barr virus; lymphoma, large B-cell, diffuse; nuclear factor kappa B; prognosis

DOI：

10.7507/1002-0179.202502138

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Objective To evaluate the expression level of nuclear factor kappa B (NF-κB) in patients with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL), and to examine its impact on patients’ clinical characteristics and prognosis. Methods Patients with EBV-positive DLBCL who were diagnosed and treated at West China Hospital of Sichuan University between January 2010 and December 2020 were selected as the research subjects. Clinical data were retrospectively collected. According to the expression of NF-κB, the patients were divided into an NF-κB-positive group and an NF-κB-negative group, and the clinical characteristics were compared between the two groups. Kaplan-Meier method was used for survival analysis. Results A total of 414 patients with DLBCL were collected, and EBV-encoded small RNAs were positive in 37 cases (8.9%). Among the 37 EBV-positive patients, NF-κB positivity was observed in 13 cases (35.1%), while among the 377 EBV-negative patients, NF-κB positivity was observed in 144 cases (38.2%), without statistically significant difference (χ²=0.134, P=0.714). No significant difference in clinical characteristics was found between the NF-κB-positive group and the NF-κB-negative group of EBV-positive patients (P>0.05). The 3-year overall survival (OS) rates for the NF-κB-positive and NF-κB-negative groups were 46.2% and 58.3%, respectively, the 5-year OS rates were 19.2% and 29.2%, respectively, and the median OS was 32 vs. 39 months (P=0.441). The corresponding 3-year and 5-year progression-free survival (PFS) rates were 46.2% vs. 41.7% and 19.2% vs. 20.8%, respectively, and the median PFS was 31 vs. 24 months (P=0.933). Conclusion There is no difference in the expression of NF-κB between EBV-positive and EBV-negative DLBCL patients, and the expression of NF-κB has no impact on the clinical characteristics or the prognosis of EBV-positive DLBCL patients.

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2.	Hwang J, Suh CH, Won Kim K, et al. The incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma: a systematic review and meta-analysis. Cancers (Basel), 2021, 13(8): 1785.
3.	Odqvist L, Montes-Moreno S, Sánchez-Pacheco RE, et al. NFκB expression is a feature of both activated B-cell-like and germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. Mod Pathol, 2014, 27(10): 1331-1337.
4.	Imbert V, Peyron JF. NF-κB in hematological malignancies. Biomedicines, 2017, 5(2): 27.
5.	Calado DP, Zhang B, Srinivasan L, et al. Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell, 2010, 18(6): 580-589.
6.	Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia, 2022, 36(7): 1703-1719.
7.	中国抗癌协会淋巴瘤专业委员会, 中国医师协会肿瘤医师分会, 中国医疗保健国际交流促进会肿瘤内科分会. 中国淋巴瘤治疗指南(2021 年版). 中华肿瘤杂志, 2021, 43(7): 707-735.
8.	Klimowicz AC, Gascoyne RD, Connors JM, et al. International prognostic index for non-Hodgkin’s lymphoma. N Engl J Med, 1995, 332(1): 58-65.
9.	Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol, 2014, 32(27): 3059-3068.
10.	Beltran BE, Castro D, Paredes S, et al. EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk-stratification and management. Am J Hematol, 2020, 95(4): 435-445.
11.	Oyama T, Ichimura K, Suzuki R, et al. Senile EBV⁺ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol, 2003, 27(1): 16-26.
12.	Battle-Lopez A, Gonzalez de Villambrosia S, Nuñez J, et al. Epstein-Barr virus-associated diffuse large B-cell lymphoma: diagnosis, difficulties and therapeutic options. Expert Rev Anticancer Ther, 2016, 16(4): 411-421.
13.	Aladily TN, Mansour AT, Mahgoob R, et al. Epstein - Barr virus infection in de novo diffuse large B-cell lymphoma in Jordan and Turkey. Ann Diagn Pathol, 2019, 43: 151406.
14.	叶云霞, 张文燕, 李甘地, 等. 中国西南地区老年人 EB 病毒阳性弥漫大 B 细胞淋巴瘤的临床病理特点及预后分析. 四川大学学报(医学版), 2014, 45(4): 652-627.
15.	叶明, 李泽霖, 闫淑芳, 等. EB 病毒阳性弥漫大 B 细胞淋巴瘤的临床病理特征. 华中科技大学学报(医学版), 2023, 52(1): 83-87.
16.	Kaileh M, Sen R. NF-κB function in B lymphocytes. Immunol Rev, 2012, 246(1): 254-271.
17.	Gebauer N, Gebauer J, Hardel TT, et al. Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly. Leuk Lymphoma, 2015, 56(4): 1100-1106.
18.	Forte E, Salinas RE, Chang C, et al. The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells. J Virol, 2012, 86(12): 6889-6898.
19.	Montes-Moreno S, Odqvist L, Diaz-Perez JA, et al. EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol, 2012, 25(7): 968-982.
20.	Ok CY, Li L, Xu-Monette ZY, et al. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries. Clin Cancer Res, 2014, 20(9): 2338-2349.
21.	刘真真, 殷莉. 影响弥漫性大 B 细胞淋巴瘤患者预后相关因素分析. 临床研究, 2023, 31(11): 1-4.
22.	Zhao J, Zhang W, Zhou D. Primary extranodal diffuse large B-cell lymphoma in the rituximab era: a single center, retrospective analysis. Hematology, 2022, 27(1): 757-764.
23.	Wu H, Zou L, Jin Y, et al. Rituximab induces ferroptosis and RSL3 overcomes rituximab resistance in diffuse large B-cell lymphoma cells. Arch Biochem Biophys. 2024, 761: 110188.

1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, 2016, 127(20): 2375-2390.
2. Hwang J, Suh CH, Won Kim K, et al. The incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma: a systematic review and meta-analysis. Cancers (Basel), 2021, 13(8): 1785.
3. Odqvist L, Montes-Moreno S, Sánchez-Pacheco RE, et al. NFκB expression is a feature of both activated B-cell-like and germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. Mod Pathol, 2014, 27(10): 1331-1337.
4. Imbert V, Peyron JF. NF-κB in hematological malignancies. Biomedicines, 2017, 5(2): 27.
5. Calado DP, Zhang B, Srinivasan L, et al. Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell, 2010, 18(6): 580-589.
6. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia, 2022, 36(7): 1703-1719.
7. 中国抗癌协会淋巴瘤专业委员会, 中国医师协会肿瘤医师分会, 中国医疗保健国际交流促进会肿瘤内科分会. 中国淋巴瘤治疗指南(2021 年版). 中华肿瘤杂志, 2021, 43(7): 707-735.
8. Klimowicz AC, Gascoyne RD, Connors JM, et al. International prognostic index for non-Hodgkin’s lymphoma. N Engl J Med, 1995, 332(1): 58-65.
9. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol, 2014, 32(27): 3059-3068.
10. Beltran BE, Castro D, Paredes S, et al. EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk-stratification and management. Am J Hematol, 2020, 95(4): 435-445.
11. Oyama T, Ichimura K, Suzuki R, et al. Senile EBV⁺ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol, 2003, 27(1): 16-26.
12. Battle-Lopez A, Gonzalez de Villambrosia S, Nuñez J, et al. Epstein-Barr virus-associated diffuse large B-cell lymphoma: diagnosis, difficulties and therapeutic options. Expert Rev Anticancer Ther, 2016, 16(4): 411-421.
13. Aladily TN, Mansour AT, Mahgoob R, et al. Epstein - Barr virus infection in de novo diffuse large B-cell lymphoma in Jordan and Turkey. Ann Diagn Pathol, 2019, 43: 151406.
14. 叶云霞, 张文燕, 李甘地, 等. 中国西南地区老年人 EB 病毒阳性弥漫大 B 细胞淋巴瘤的临床病理特点及预后分析. 四川大学学报(医学版), 2014, 45(4): 652-627.
15. 叶明, 李泽霖, 闫淑芳, 等. EB 病毒阳性弥漫大 B 细胞淋巴瘤的临床病理特征. 华中科技大学学报(医学版), 2023, 52(1): 83-87.
16. Kaileh M, Sen R. NF-κB function in B lymphocytes. Immunol Rev, 2012, 246(1): 254-271.
17. Gebauer N, Gebauer J, Hardel TT, et al. Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly. Leuk Lymphoma, 2015, 56(4): 1100-1106.
18. Forte E, Salinas RE, Chang C, et al. The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells. J Virol, 2012, 86(12): 6889-6898.
19. Montes-Moreno S, Odqvist L, Diaz-Perez JA, et al. EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol, 2012, 25(7): 968-982.
20. Ok CY, Li L, Xu-Monette ZY, et al. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries. Clin Cancer Res, 2014, 20(9): 2338-2349.
21. 刘真真, 殷莉. 影响弥漫性大 B 细胞淋巴瘤患者预后相关因素分析. 临床研究, 2023, 31(11): 1-4.
22. Zhao J, Zhang W, Zhou D. Primary extranodal diffuse large B-cell lymphoma in the rituximab era: a single center, retrospective analysis. Hematology, 2022, 27(1): 757-764.
23. Wu H, Zou L, Jin Y, et al. Rituximab induces ferroptosis and RSL3 overcomes rituximab resistance in diffuse large B-cell lymphoma cells. Arch Biochem Biophys. 2024, 761: 110188.

West China Medical Journal

Latest ArticlesExpression of nuclear factor kappa B and its correlation with prognosis in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma

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