EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions

Deng, Yujie; Chen, Xiaohui; Huang, Chuanzhong; Chen, Gang; Chen, Fangfang; Lu, Jianping; Shi, Xi; He, Cheng; Zeng, Zhiyong; Qiu, Yanhua; Chen, Junqiang; Lin, Rongbo; Chen, Yanping; Chen, Junmin

doi:10.7150/jca.29807

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J Cancer 2019; 10(9):2006-2017. doi:10.7150/jca.29807 This issue Cite

Research Paper

EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions

Yujie Deng^1#, Xiaohui Chen^2#, Chuanzhong Huang³, Gang Chen⁴, Fangfang Chen⁴, Jianping Lu⁴, Xi Shi¹, Cheng He⁴, Zhiyong Zeng⁵, Yanhua Qiu⁶, Junqiang Chen⁷, Rongbo Lin⁸, Yanping Chen⁴, Junmin Chen^5✉

1. Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
2. Department of Thoracic Surgery, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
3. Laboratory of Immuno-Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
4. Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
5. Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
6. Department of Medical Imaging, Grade 2014, Fujian Medical University, Fuzhou, China
7. Department of Thoracic Radiotherapy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
8. Department of Gastrointestinal Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
# These two authors contributed equally to this paper.

Citation:

Deng Y, Chen X, Huang C, Chen G, Chen F, Lu J, Shi X, He C, Zeng Z, Qiu Y, Chen J, Lin R, Chen Y, Chen J. EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions. J Cancer 2019; 10(9):2006-2017. doi:10.7150/jca.29807. https://www.jcancer.org/v10p2006.htm

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Abstract

Enhancer of zeste homolog 2 (EZH2) and Bcl-2 gene rearrangement or protein upregulation played pivotal roles in the carcinogenesis of various malignancies including lymphomas. However, EZH2/Bcl-2 expression pattern and its clinicopathologic/prognostic significance in diffuse large B-cell lymphoma (DLBCL) remain unclear. To identify the association among EZH2, Bcl-2, clinicopathologic parametres in DLBCL, 2 DLBCL patient sets (test cohort, n=85; validation cohort n=51) and DLBCL cell lines were studied by tumor tissue microarray (TMA), immunohistochemistry and western blot. The optimal cut-off of EZH2 was determined by X-tile program from test cohort, as was verified in validation cohort. The prognostic significance was determined via Kaplan-Meier survival estimates and log-rank tests. Consequently, EZH2 and Bcl-2 expression were both enhanced and positively correlated with each other (𝑃=0.001) in both DLBCL patients and cell lines. EZH2/Bcl-2 coexpression was associated with poor overall survival (OS) and progression-free survival (PFS) in all DLBCL patients (all P<0.05). Univariate analyses revealed that EZH2/Bcl-2 coexpression correlated to worse objective response rate (ORR), shorter OS and PFS in DLBCL patients treated with RCHOP while multivariate analysis indicated that only elevated LDH level (P=0.001) and presence of B symtom (P=0.008) rather than EZH2/Bcl-2 coexpression were associated with worse OS. No survival benefit from rituximab regimen had been demonstrated in the early-staged DLBCL patients with EZH2/Bcl-2 coexpression. While in the subgroup of III-IV stage, RCHOP regimen showed obvious better OS and PFS than CHOP (P=0.039 and 0.005). In conclusion, EZH2/Bcl-2 coexpression defines unrecognized subgroup of DLBCL patients with distinct epigenetic phenotype and worse outcome.

Keywords: diffuse large B-cell lymphoma·EZH2·Bcl-2·prognosis·rituximab

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APA

Deng, Y., Chen, X., Huang, C., Chen, G., Chen, F., Lu, J., Shi, X., He, C., Zeng, Z., Qiu, Y., Chen, J., Lin, R., Chen, Y., Chen, J. (2019). EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions. Journal of Cancer, 10(9), 2006-2017. https://doi.org/10.7150/jca.29807.

ACS

Deng, Y.; Chen, X.; Huang, C.; Chen, G.; Chen, F.; Lu, J.; Shi, X.; He, C.; Zeng, Z.; Qiu, Y.; Chen, J.; Lin, R.; Chen, Y.; Chen, J. EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions. J. Cancer 2019, 10 (9), 2006-2017. DOI: 10.7150/jca.29807.

NLM

CSE

Deng Y, Chen X, Huang C, Chen G, Chen F, Lu J, Shi X, He C, Zeng Z, Qiu Y, Chen J, Lin R, Chen Y, Chen J. 2019. EZH2/Bcl-2 Coexpression Predicts Worse Survival in Diffuse Large B-cell Lymphomas and Demonstrates Poor Efficacy to Rituximab in Localized Lesions. J Cancer. 10(9):2006-2017.

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