Deubiquitinase OTUD7B is a potential prognostic biomarker in diffuse large B-cell lymphoma

Abstract

OTUD7B is a deubiquitinase and has been reported as a prognostic factor in various solid tumors. However, its prognostic value in lymphoma patients remains unclear. We detected OTUD7B expression levels in 160 diffuse large B-cell lymphoma (DLBCL) tissue samples by immunohistochemistry, and analyzed correlations between its expression and clinic-pathologic parameters as well as clinical outcomes. We also investigated association between OTUD7B expression and chemotherapeutic drugs anti-tumor activity in vitro. We found that OTUD7B overexpressed in 129 (80.6%) cases, and patients with overexpression of OTUD7B experienced better overall survival comparing to those with OTUD7B low expression (P=0.021). Multivariate Cox regression analysis illustrated that OTUD7B was an independent prognostic indicator. In DLBCL cell lines, we found that Chidamide could up-regulate OTUD7B in several DLBCL cell lines, and also had synergistic effect with doxorubicin at low concentration. Our data illustrated that OTUD7B deficiency is a negative predictor of clinical outcome, and might be a potential therapeutic target in the treatment of diffuse large B-cell lymphoma.

AtomNet-Aided OTUD7B Inhibitor Discovery and Validation

“…In addition to NSCLC, overexpression of OTUD7B was also observed in diffuse large B-cell lymphoma [30] and served as a prognostic marker. This promoted us to examine the roles of OTUD7B in leukemia cells.…”

“…Increased OTUD7B expression is observed in breast cancer [28] and lung cancer [29]. OTUD7B is a prognostic maker in diffuse large B-cell lymphoma [30] and NSCLC [31], as well as a potential therapeutic target for myocardial infarction by ameliorating fibrosis [32], and predicts poor responses to paclitaxel in TNBC [28]. Considering its oncogenic function in cancer and its great potential as a cancer drug target but without available inhibitors, here we aim to rely on artificial intelligence AtomNet to screen for small molecule OTUD7B inhibitors.…”

OTU deubiquitinase 7B facilitates the hyperthermia‐induced inhibition of lung cancer progression through enhancing Smac‐mediated mitochondrial dysfunction

“…43 This is consistent with the higher activity of the apoptotic factor caspase-3 in the present study, suggesting that upregulation of OTUD7B may synergize the pro-apoptotic effects of hyperthermia. Qiu et al 17 identified OTUD7B as an independent prognostic marker for diffuse large B-cell lymphoma with a synergistic effect on doxorubicin (DOX). These lines of evidence all point to the antitumor activity of OTUD7B.…”

“…OTU deubiquitinase 7B (OTUD7B) is a member of the OTU family. As a deubiquitinating enzyme (DUB), it regulates many important cellular signaling pathways, such as those related to inflammation, scar formation, and T cell activation 16,17 . Accumulating data suggested that OTUD7B expression directly affected the survival rate of various solid tumors, such as lung cancer, liver cancer, breast cancer, or pancreatic cancer, and played a potential role in cancer cell proliferation 18–21 .…”

“…As a deubiquitinating enzyme (DUB), it regulates many important cellular signaling pathways, such as those related to inflammation, scar formation, and T cell activation. 16,17 Accumulating data suggested that OTUD7B expression directly affected the survival rate of various solid tumors, such as lung cancer, liver cancer, breast cancer, or pancreatic cancer, and played a potential role in cancer cell proliferation. [18][19][20][21] It has recently been shown that OTUD7B attenuates the ubiquitination level of N1ICD (Notch1 intracellular domain) by binding to RHBDL2 (rhomboid-like 2 protein), thereby activating Notch signaling.…”