Deubiquitinase OTUD7B Is Potential Prognostic Biomarker in Diffuse Large B-Cell Lymphoma

Abstract

Background: Diffuse Large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma and most patients can be cured under immune-chemotherapy. One third of patients will relapse and acquired resistance to chemotherapy and turned to uncurable. The identification of biomarkers of clinical behavior may aid in the implementation of novel therapeutic strategies. OTUD7B is a deubiquitinase and is a pivotal regulator of the noncanonical NF-κB pathway. The deficiency of OTUD7B can activate the noncanonical NF-κB pathway and mediate important biological functions, including lymphoid organogenesis, B lymphocyte function, and cell growth and survival. Activation of NF-κB pathway has been an adverse prognostic index in DLBCL. The prognostic value of OTUD7B expression in lymphoma patients remains unclear. We conducted a retrospective study to investigate the impact of OTUD7B expression in DLBCL patients. Methods: Histologically confirmed DLBCL patients (N=100) treated at Fudan University Shanghai Cancer Center with available diagnostic biopsy material were identified. Forty-two patients were treated with CHOP and fifty-eight patients with R-CHOP. OTUD7B expression was determined and quantified by immunohistochemistry (IHC) with the percentage of positive cells. Tumors were considered positive when at least 20% of tumor cells expressed OTUD7B. Kaplan-Meier method was used to calculate progression free survival (PFS) and overall survival (OS) and curves were compared with the long-rank test in both groups. Correlation between the OTUD7B expression and clinical variables were tested by Pearson Chi Square test and a two-sided P value of <0.05 was considered to be statistically significant. Result: the OTUD7B expression was detected in 79/100(79%) DLBCL patients and 21% patients shown OTUD7B deficiency. It seems the OTUD7B positive patients had a better outcome, But there was no significance (p=0.107), The PFS and OS were 81% and 85% in OTUD7B positive group and 67% and 72% in OTUD7B negative group. In patients treated with CHOP regimen, the OTUD7B deficiency was associated with a worse PFS compared with OTUD7B positive patients (20% vs 78%, p=0.004). the OS of OTUD7B deficiency patients also shown a worse trend compared with the positive group (40% vs 79%, p=0.057). In patients treated with R-CHOP regimen, it is surprising, no differences between the OTUD7B positive group and negative groups were observed in terms of PFS or OS. Rituximab may overcome this worse effect caused by OTUD7B deficiency. The OTUD7B deficiency were 15% in GCB patients and 25% in non-GCB patients (p=0.31). The basic characteristics were no difference between OTUD7B positive and negative groups. Conclusion: This is the first report demonstrating that, OTUD7B deficiency is a negative predictor of clinical outcome. OTUD7B is a potential novel target to treat lymphoma and further investigation of OTUD7B need to be done in the near future. (Research supported by National Natural Science Foundation of China (no.81670177, no.81001048). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.