Index For Diffuse Large B-cell Lymphoma Research Articles

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma

ABSTRACT Background Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). Methods We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. Results The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. Conclusion The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Evaluation of the Proliferative Activity of Diffuse Large B-Cell Lymphoma (DLBCL) in Dogs with Respect to Patient Eligibility for Anthracycline-Based Chemotherapy.

Simple SummaryCanine lymphomas usually have aggressive behavior, but respond well to chemotherapy. Despite proper diagnosis and numerous available therapeutic regimens, it is difficult to determine the prognosis and choose the optimal method of treatment in each individual patient. Diffuse large B-cell lymphoma is the most commonly diagnosed histological subtype of canine lymphoma and is treated with anthracyclines alone or in combination with other chemotherapeutics. A new diagnostic marker of prognostic and predictive value is topoisomerase IIα, which also constitutes a molecular target for anti-cancer drugs belonging to the group of topoisomerase IIα inhibitors including anthracyclines. Proliferative activity was estimated in samples of enlarged lymph nodes in dogs with diffuse large B-cell lymphoma based on mitotic count and immunohistochemical evaluation of topoisomerase IIα and Ki67 antigen expression with a view to qualifying patients for anthracycline-base chemotherapy. It has been shown that higher levels of topoisomerase IIα expression corresponded to a higher mitotic count but not to Ki67 index. These results indicate that an immunohistochemical evaluation of topoisomerase IIα expression can be used to develop a diagnostic-clinical protocol for the treatment of dogs with diffuse large B-cell lymphoma using anthracycline-based chemotherapy.Different types of canine lymphoma respond differently to chemotherapy and have different prognoses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in dogs. Topoisomerase II alpha (TOPIIα) protein has been shown to be a proliferation marker associated with prognostic significance. The aim of the study was to determine the relationship between TOPIIα expression, mitotic count (MC), and Ki67 antigen index in DLBCL in dogs, taking into account the applicability of these parameters to select the chemotherapy protocol with emphasis on the use of anthracycline drugs. Samples of formalin-fixed paraffin-embedded lymph nodes from 34 dogs with DLBCL were immunohistochemically labelled with anti-TOPIIα and Ki67. The number of positive cells and the intensity of the reaction were taken into account in order to assess TOPIIα expression. MC was estimated in the hematoxylin and eosin-stained slides in the area of 2.37 mm2. Positive association between TOPIIα and MC, but no association between TOPIIα and Ki67 was found. It can be concluded that the immunohistochemical determination of TOPIIα as a molecular target for drugs from the anthracycline group may be used in association with MC to establish a diagnostic-clinical protocol for selecting dogs with DLBCL for treatment with anthracycline drugs.

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

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.

Prognostic Significance of Bcl-2 and p53 Protein Expressions and Ki67 Proliferative Index in Diffuse Large B-cell Lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) is a high-grade neoplasm that has heterogeneous properties in clinical, morphological, and immunophenotypic aspects. In the present study the effects of p53, Bcl-2, and Ki67 on prognosis and their relationships with clinical parameters were examined. Materials and Methods: Thirty-five patients who had been diagnosed with nodally located DLBCL at İzmir Atatürk Training and Research Hospital between January 1999 and June 2006 were included in the study. The Ann Arbor classification system was used to determine the stage of the patients. The patients were evaluated according to age, sex, stage, B symptoms, extranodal involvement, and lactate dehydrogenase (LDH) level as well as immunohistochemically. P53 protein and Bcl-2 oncoprotein expressions and Ki67 proliferation index were assessed immunohistochemically. Results: High Bcl-2 expression was found in 9 patients (25.7%), high p53 expression was found in 10 patients (28.6%), and high Ki67 was observed in 23 patients (65.7%). There was no significant correlation between p53 expression, Bcl-2 expression, or Ki67 proliferation index and age, sex, stage, B symptoms, extranodal involvement, LDH level, and overall survival (p>0.05). We did not find a relationship among p53 expression, Bcl-2 expression, Ki67 proliferation index, and prognosis (p>0.05). There was no significant relationship between overall survival and age, sex, stage, B symptoms, extranodal involvement, or LDH level (p>0.05). Our results revealed that Bcl-2 and p53 protein expressions and Ki67 proliferation index have no effect on overall survival of patients with DLBCL.Conclusion: The prognostic importance of p53 and Bcl-2 protein expressions and Ki67 proliferation index in DLBCL, which has biological and clinical heterogeneity, can be understood in a large series of studies that have subclasses and immunohistochemical markers with optimal cut-off values.