scholarly journals Increased Malat1 Expression Predicts Poor Prognosis in Primary Gastrointestinal Diffuse Large B-cell Lymphoma

Author(s):  
Zhengzi Qian ◽  
Leiyuan Chen ◽  
Xinyuan Wang ◽  
Yutian Kan ◽  
Yafei Wang ◽  
...  

Abstract Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been involved in the pathogenesis and progression of several cancers. However, the exact effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in PGI-DLBCL patients. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably up-regulated in PGI-DLBCL tissues as compared to that of paired adjacent non-tumor tissues (P<0.001), and the area under the ROC curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB) group, advanced stage (stages IIE-IV) group and International Prognostic Index (IPI) score (3-5) group (P=0.01, P<0.001and P<0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression was correlated with inferior Overall survival (OS) and progression free survival (PFS) in PGI-DLBCL patients (P<0.001and P<0.001, respectively), and multivariate analysis suggested that up-regulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors of PGI-DLBCL. In conclusion, our results demonstrates that MALAT1 might serve as a novel prognostic biomarker and an ideal therapeutic target for PGI-DLBCL patients in the future.

2019 ◽  
Vol 72 (1-2) ◽  
pp. 25-29
Author(s):  
Maja Popovic ◽  
Gorana Matovina-Brko ◽  
Dragana Petrovic ◽  
Bojana Vranjkovic ◽  
Jelena Radic ◽  
...  

Introduction. The research aimed to evaluate the impact of age-adjusted international prognostic index and time to the first relapse on overall survival and progression-free survival from the beginning of the second line of treatment in patients with relapsed/ refractory diffuse large B-cell lymphoma. Material and Methods. The research included 36 patients with relapsed/refractory diffuse large B-cell lymphoma treated at the Oncology Institute of Vojvodina, Serbia, from January 2013 to December 2015. Patients were stratified according to age-adjusted international prognostic index score at the time of relapse into patients with low risk (score 0 - 1) and patients with high risk (score 2 - 3), as well as according to the time of the first relapse: early relapse (? 12 months) and late relapse (> 12 months). Results. In the group of patients with a score of 0 - 1, the median overall survival was 44 months compared with 6 months in patients with score of 2 - 3, hazard ratio 0,4 (confidence interval 0,16 - 0,99), p = 0,03. In patients with early relapse, the median overall survival was 7 months compared with 25 months in patients with late relapse, hazard ratio 0,55 (confidence interval 0,25 - 1,19), p = 0,12. In patients with early relapse, median progression-free survival was 0 months compared with 10 months in patients with late relapse, hazard ratio 0,34 (confidence interval 0,12 - 1,00), p = 0,0017. Conclusion. The impact of age-adjusted international prognostic index score significantly affects overall survival in patients with relapsed diffuse large B-cell lymphoma. The time to the first relapse impacts progression-free survival calculated from the time of the second-line treatment initiation.


2008 ◽  
Vol 26 (19) ◽  
pp. 3189-3195 ◽  
Author(s):  
Kazuyuki Shimada ◽  
Kosei Matsue ◽  
Kazuhito Yamamoto ◽  
Takuhei Murase ◽  
Naoaki Ichikawa ◽  
...  

Purpose To evaluate the safety and efficacy of rituximab-containing chemotherapies for intravascular large B-cell lymphoma (IVLBCL). Patients and Methods We retrospectively analyzed 106 patients (59 men, 47 women) with IVLBCL who received chemotherapy either with rituximab (R-chemotherapy, n = 49) or without rituximab (chemotherapy, n = 57) between 1994 and 2007 in Japan. The median patient age was 67 years (range, 34 to 84 years). The International Prognostic Index was high-intermediate/high in 97% of patients. Results The complete response rate was higher for patients in the R-chemotherapy group (82%) than for those in the chemotherapy group (51%; P = .001). The median duration of follow-up for surviving patients was 18 months (range, 1 to 95 months). Progression-free survival (PFS) and overall survival (OS) rates at 2 years after diagnosis were significantly higher for patients in the R-chemotherapy group (PFS, 56%; OS, 66%) than for patients in the chemotherapy group (PFS, 27% with P = .001; OS, 46% with P = 0.01). Multivariate analysis revealed that the use of rituximab was favorably associated with PFS (hazard ratio [HR], 0.45; 95% CI, 0.25 to 0.80; P = .006) and OS (HR, 0.42; 95% CI, 0.21 to 0.85; P = .016). Treatment-related death was observed in three patients (6%) who received R-chemotherapy and in five patients (9%) who received chemotherapy. Conclusion Our data suggest improved clinical outcomes for patients with IVLBCL in the rituximab era. Future prospective studies of rituximab-containing chemotherapies are warranted.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3447-3447
Author(s):  
Daisuke Ennishi ◽  
Masahiro Yokoyama ◽  
Kengo Takeuchi ◽  
Hiroaki Asai ◽  
Yuko Mishima ◽  
...  

Abstract Background: Several biomarkers indicating poor prognosis have been reassessed in patients with diffuse large B-cell lymphoma (DLBCL) treated by rituximab combination chemotherapy. However, no studies have investigated the outcome by combining these biomarkers for rituximab treatment. In addition, no large studies have reassessed the outcome of patients with CD5-positive DLBCL treated by rituximab. To determine the most influential biomarkers, we reassessed and investigated the predictive value of three biomarkers, namely Bcl-2 expression, GC phenotype and CD5 expression, in DLBCL patients treated with rituximab in combination with CHOP as an initial therapy. Methods: A total of 121 patients with CD20-positive DLBCL receiving RCHOP at our institute between April 2002 and October 2005 were enrolled in the study. To classify the samples into immunohistochemically defined GC or non-GC phenotypes, we used a previously described algorithm using expression of CD10, Bcl-6, and MUM1 (Hans et al. Blood, 2004). For examination of the CD5 expression, we defined the cases as CD5-positive if CD5 expression was detected by immunohistochemical and flow cytometric analyses. We also assessed the outcome of patients according to International Prognostic Index (IPI). Results: Expression of Bcl-2 was detected in 79 of the 121 (65%) patients, while CD5 expression was positive in 11 patients (9%). Overall, 48 of the 121 (40%) patients expressed a non-GC phenotype. CD5-positive patients displayed a significantly poorer progression-free survival (PFS) and overall survival (OS) than CD5-negative patients (2-year PFS, 18% vs. 73%, P<0.001; OS, 45% vs. 91%, P=0.001). However, there were no significant differences in PFS and OS according to Bcl-2 expression (PFS, 76% vs. 91%, P=0.08; OS, 77% vs. 97%, P=0.06) or GC phenotype (PFS, 70% vs. 90%, P=0.08; OS, 77% vs. 91%, P=0.12). In contrast, the differences between high or high-intermediate and low or low-intermediate of IPI for PFS and OS were significant (2-year PFS, 52% vs. 91%, P=0.001; OS, 64% vs. 92%, P=0.01). Multivariate analysis revealed that CD5 expression and the IPI were significant prognostic factors for PFS and OS (RR: PFS, 13.57 and 9.65, respectively; OS, 18.15 and 10.72, respectively) (Table 1). Conclusion: These results demonstrated that CD5 expression was the most influential prognostic factor among the biomarkers examined and associated with a very poor outcome, even after rituximab treatment. To confirm this conclusion, further large studies of CD5-positive DLBCL patients are required. Cox’s hazard regression analysis of PFS and OS Variable RR 95% CI P RR indicates relative risk; CI, confidence interval; GC phenotype, non-GC type worse; and IPI, higher IPI worse PFS CD5 13.57 4.260–42.947 <0.001 BCL2 2.00 0.518–7.761 0.314 GC phenotype 2.59 0.851–7.857 0.094 IPI 0 to2 or 3 to 5 9.65 2.911–31.987 <0.001 OS CD5 18.15 3.023–109.029 0.002 BCL2 1.29 0.240–6.966 0.764 GC phenotype 1.43 0.367–5.573 0.606 IPI 0 to2 or 3 to 5 10.72 1.945–59.085 0.006


Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 1857-1861 ◽  
Author(s):  
Laurie H. Sehn ◽  
Brian Berry ◽  
Mukesh Chhanabhai ◽  
Catherine Fitzgerald ◽  
Karamjit Gill ◽  
...  

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers. Since randomized controlled trials of R-CHOP in DLBCL have included select subgroups of patients, the utility of the International Prognostic Index (IPI) has not been reassessed. We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy. The IPI remains predictive, but it identifies only 2 risk groups. Redistribution of the IPI factors into a revised IPI (R-IPI) provides a more clinically useful prediction of outcome. The R-IPI identifies 3 distinct prognostic groups with a very good (4-year progression-free survival [PFS] 94%, overall survival [OS] 94%), good (4-year PFS 80%, OS 79%), and poor (4-year PFS 53%, OS 55%) outcome, respectively (P < .001). The IPI (or R-IPI) no longer identifies a risk group with less than a 50% chance of survival. In the era of R-CHOP treatment, the R-IPI is a clinically useful prognostic index that may help guide treatment planning and interpretation of clinical trials.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.


2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.


2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 271-271
Author(s):  
Ryan James Chan ◽  
Rasna Gupta ◽  
Sindu Mary Kanjeekal ◽  
Mohammed Jarrar ◽  
Amin Kay ◽  
...  

271 Background: The Windsor Regional Cancer Program (WRCP) was determined to have consistently been a top performer in time to treatment of diffuse large B cell lymphoma in this Canadian province (http://www.csqi.on.ca/by_type_of_cancer/lymphoma/lymphoma_treatment/). We endeavored to determine whether faster time to diagnosis and treatment for diffuse large B-cell lymphoma (DLBCL) influenced the IPI score (International Prognostic Score), thereby predicting an improved clinical outcome in these presenting patients. Methods: The WRCP services a catchment area of 650,000 people. A retrospective chart review was conducted for patients diagnosed with DLBCL at the Windsor Regional Cancer Program (WRCP) between 2006-2012. Information collected included the five factors for scoring by the International Prognostic Index (IPI) – age, performance status, LDH, stage, and number of extranodal sites – chemotherapy regimen, relapses, existence of second malignancies, cause of death, and dates of diagnosis, last follow-up, and death. We analyzed the relationship between prognostic factors and these clinical outcomes, and also compared the IPI scores for this cohort of patients against a similar population in another Canadian province, British Columbia. Results: It is established that compared to other cancer centres in Ontario, the WRCP is consistently reporting a shorter diagnosis to treatment metric when compared to their counterparts in Ontario, Canada. When compared to historical Canadian data, presenting IPI scores for DLBCL patients were lower on average for patients treated at the WRCP than those reported in British Columbia, Canada by Sehn et al. [Sehn, L. H., et al. (2007). The revised International Prognostic Index is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood, 109(5), 1857-1861.]. Conclusions: A lower presenting IPI score is known to be correlated improved lymphoma related outcome. With attention to the metric of diagnosis to treatment < 30 days for diffuse large B cell lymphoma, we expect an improved lymphoma related outcome for our patients. We recommend ongoing attention to this metric, in order to improve outcomes for our patients.


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