Abstract:Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restri… Show more
“…The NOS scores in the column titled “Comparability of Cohorts on the Basis of the Design or Analysis” indicate that some of the studies provided details regarding their design. In the studies by M Rengasamy, 27 Y Wu, 31 Lu Ge 20 , YH Li, 37 AK Schnormeier, 28 G Walbrecq, 29 W Barczak, 10 Bajbouj K, 40 and Gao J, 42 authors used RNA-Seq data from public database, such as TCGA, GEO, METABRIC data, but the authors did not provide study design of the included patients as well as the follow-up time, hence, a star could not be awarded. According to the assessment results, the studies included in this meta-analysis were considered high-quality studies.…”
Section: Resultsmentioning
confidence: 99%
“…Among the left 35 articles, 3 articles could not be used to extract HRs and 95% CIs from the survival curves. Finally, 32 articles were included, 5,8-13,19-43 those articles were published between January 1, 2013 and July 25, 2021. The flow diagram was shown in Figure 1.Figure 1.Flow diagram of the study selection in the meta-analysis.…”
Purpose Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features. Methods Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle–Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data. Results A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, P =.008; I2 = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, P < .001; I2 = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, P < .001; I2 = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer. Conclusion For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.
“…The NOS scores in the column titled “Comparability of Cohorts on the Basis of the Design or Analysis” indicate that some of the studies provided details regarding their design. In the studies by M Rengasamy, 27 Y Wu, 31 Lu Ge 20 , YH Li, 37 AK Schnormeier, 28 G Walbrecq, 29 W Barczak, 10 Bajbouj K, 40 and Gao J, 42 authors used RNA-Seq data from public database, such as TCGA, GEO, METABRIC data, but the authors did not provide study design of the included patients as well as the follow-up time, hence, a star could not be awarded. According to the assessment results, the studies included in this meta-analysis were considered high-quality studies.…”
Section: Resultsmentioning
confidence: 99%
“…Among the left 35 articles, 3 articles could not be used to extract HRs and 95% CIs from the survival curves. Finally, 32 articles were included, 5,8-13,19-43 those articles were published between January 1, 2013 and July 25, 2021. The flow diagram was shown in Figure 1.Figure 1.Flow diagram of the study selection in the meta-analysis.…”
Purpose Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features. Methods Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle–Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data. Results A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, P =.008; I2 = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, P < .001; I2 = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, P < .001; I2 = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer. Conclusion For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.
“…As previously described in AML, treatment with a PRMT5 inhibitor impairs DNA repair mechanisms in CLL cell lines. This effect is enhanced when combined with a PARP inhibitor, leading to increased cell death [ 111 ].…”
Section: Pharmacological Inhibition Of Prmts In Hematological Maligna...mentioning
Arginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they form on a molecule of arginine. During the formation and maturation of the different types of blood cells, PRMTs play a central role by controlling cell differentiation at the transcriptional level. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails’ arginine. Chemical tools have been developed to inhibit the activity of PRMTs and have been tested in several models of hematological malignancies, including primary samples from patients, xenografts into immunodeficient mice, mouse models, and human cell lines. They show a significant effect by reducing cell viability and increasing the overall survival of mice. PRMT5 inhibitors have a strong therapeutic potential, as phase I clinical trials in hematological malignancies that use these molecules show promising results, thus, underlining PRMT inhibitors as useful therapeutic tools for cancer treatment in the future.
“…This suggests that DAD1, together with other abnormally expressed proteins, may be a potential biomarker of SPTP in clinical therapy. High expression levels and high variability of DAD1 have also been determined in chronic lymphocytic luekemia, one of the non-solid tumors ( 95 ).…”
Section: Overview Of Dad1 and Its Cancerous Rolementioning
As key regulators of apoptosis, BAD and defender against apoptotic cell death 1 (DAD1) are associated with cancer initiation and progression. Multiple studies have demonstrated that BAD and DAD1 serve critical roles in several types of cancer and perform various functions, such as participating in cellular apoptosis, invasion and chemosensitivity, as well as their role in diagnostic/prognostic judgement, etc. Investigating the detailed mechanisms of the cancerous effects of the two proteins will contribute to enriching the options for targeted therapy, and may improve clinical treatment of cancer. The present review summarizes research advances regarding the associations of BAD and DAD1 with cancer, and a hypothesis on the feasible relationship and interaction mechanism between the two proteins is proposed. Furthermore, the present review highlights the potential of the two proteins as therapeutic targets and valuable diagnostic and prognostic biomarkers.
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