Elevated PRKD2 Promotes Progression and Poor Prognosis of Multiple Myeloma
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PROVIDER: PRJNA1117013 | ENA |
REPOSITORIES: ENA
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Project description:Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
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Project description:This study aimed to address the challenges in treating multiple myeloma (MM) and its advanced stage, relapsed and refractory multiple myeloma (RRMM), by identifying new therapeutic targets. Clinical data were collected from 132 MM patients. Through propensity score matching, bone marrow samples from 24 MM patients and 6 control individuals were selected for RNA sequencing analysis. Western blot validation was performed in cell lines to investigate the role of serine/threonine-protein kinase D2 (PRKD2) in MM and RRMM. Additionally, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, immune infiltration analysis, and drug sensitivity screening were conducted. The study found PRKD2 to be significantly upregulated in MM and RRMM, suggesting its potential as a therapeutic target. Functional assays indicated that disrupting PRKD2 inhibited myeloma cell proliferation, and pathway analysis revealed immune-related pathway alterations associated with PRKD2 expression. Drug sensitivity analysis identified Axitinib as a potential therapeutic agent targeting PRKD2, highlighting its promise for MM treatment.
2025-09-09 | GSE268395 | GEO
Project description:Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years. To better understand and identify these ‘high-risk’ cases, we analyzed the translocation landscape of myeloma from 795 newly-diagnosed patients by whole genome sequencing from the CoMMpass study. Translocations involving the immunoglobulin lambda (IgL) locus were identified in 10% of patients, and were indicative of poor prognosis. Importantly, 70% of IgL translocations co-occurred with hyperdiploid disease, a marker of standard risk, potentially resulting in the misclassification of IgL-translocated myeloma. Most IgL-translocations coincided with focal amplifications that were centered on the 3’ enhancer. Patients with IgL-translocations failed to benefit from immunomodulatory imide drugs (IMiDs), which target the lymphocyte-specific transcription factor IKZF1 that is bound to the IgL 3’ enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL-translocation as a driver of poor prognosis which may be due in part to IMID resistance.
2019-03-13 | GSE121912 | GEO
Project description:Myeloma is a clonal malignancy of plasma cells. Poor prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor prognosis patients and this can be improved by combination with information about DNA level changes. Using SNP-based gene mapping in combination with global gene expression analysis we have identified homozygous deletions in genes and networks that are relevant to myeloma. From these, we have generated an expression-based signature associated with shorter survival in 247 patients and confirmed this signature in data from 2 independent groups totalling 800 patients. We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the “Cell Death” network was over-represented and cases with these deletions have impaired overall survival. We defined a gene expression signature of 97 cell death genes that reflects prognosis confirmed this in two independent data sets. We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor prognosis myeloma in the clinical environment. The signature can form the basis of future trials aimed at improving the outcome of poor prognosis myeloma.
2010-03-22 | GSE15695 | GEO
Project description:Splicing Factor SRSF1 Promotes Tumorigenesis via Oncogenic Splice-Switching and Predicts Poor Prognosis in Multiple Myeloma
| PRJNA674309 | ENA
Project description:Poor prognosis for acute cerebral infarction (ACI) was suggested to be predicted using the high expression of some novel molecular markers, for example long non-coding RNAs (lncRNAs). Differentially expressed lncRNAs in peripheral whole blood from the ACI patients and healthy volunteers(HVT) were identified using microarray and further verified by qRT-PCR. The clinical outcome evaluated by 3-month modified Rankin Score (mRS), stroke stratification classified by OCSP criteria, and the expression characteristics of specific lncRNAs were analyzed in ACI patients. Among 5686 differentially expressed lncRNAs screened out by the microarray, nine were verified by qRT-PCR. Particularly, the expression of NR_120420 and lnc-GCH1-2:3 in the ACI group were significantly higher than the HVT group. ROC analysis showed that the sensitivity and specificity of NR_120420 were 85.7% and 84.6% in patients with total anterior circulation infarction (TACI) respectively(area under curve，AUC=0.861), while the sensitivity and specificity of lnc-GCH1-2:3 were 85.7% and 82.1% in patients with TACI respectively(AUC=0.802). Multivariate logistic regression showed that NR_120420 was a significantly independent diagnostic factor for ACI. The elevated expression levels of NR_120420 and lnc-GCH1-2:3 were associated with the TACI stroke classification and the poor prognosis of ACI. Our study clearly illustrated that the elevated expression levels of circulating NR_120420 and lnc-GCH1-2:3 could predict the TACI stroke classification with high sensitivity and specificity and the poor prognosis of patients with ACI.
2021-03-18 | GSE102541 | GEO
Project description:ILF2 Regulates RNA splicing of DNA Damage Response Genes to confer poor prognosis in 1q21-Amplified Multiple Myeloma
| PRJNA326671 | ENA
Project description:Purpose Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. Methods We performed a genome-wide analysis of malignant plasma cells from 192 newly myeloma patients using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. Results Our analyses revealed deletions and amplifications in 98% of cases. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis while recurrent amplifications of chromosomes 5, 9, 11, 15 and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3) and del(12p13.31). When adjusted to the established prognostic variables ie t(4;14), and serum beta2-microglobulin (Sb2M), del(12p13.31) remained the most powerful independent marker (P <.0001; hazard ratio = 3.17) followed by Sb2M (P <.0001; hazard ratio = 2.78) and amp(5q31.3) (P =.0005; hazard ratio = 0.37). Cases with amp(5q31.3) alone and low Sb2M had an excellent prognosis (5-year overall survival = 87%) conversely cases with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sb2M had a very poor outcome (5-year overall survival = 20%). Moreover, integration of SNP mapping and gene expression identified CD27 as potential critical gene responsible for poor prognosis of del(12p) myeloma patients. Conclusion These findings demonstrate the power and accessibility of molecular karyotyping to identify novel strong independent prognostic markers: amp(5q31.3) and del(12p13.31) and to provide insights into putative pathways deregulated in sub classes of cancer patients. Keywords: Human chromosome copy-number alterations study 192 myeloma patients at diagnosis examined with 500K Set Affymetrix chips
2009-08-19 | E-GEOD-12896 | biostudies-arrayexpress
Project description:Aberrant hyperediting of myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis
| PRJNA433846 | ENA
Project description:Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in multiple myeloma (MM) development have not yet been elucidated. We identified SRSF1 as a key splicing factor in tumor progression, SRSF1 expression was frequently upregulated in MM and correlated with poor survival.We conducted transcriptome comparison of SRSF1-knockdown and control cells highlighted the functional importance of SRSF1 in mediating MM progression through regulating AS, and revealed the upstream and downstream molecular regulation mechanism of SRSF1. Further investigation to clarify molecular mechanisms and to replicate our findings is necessary. Thus, our findings are of high translational relevance and are expected to have a substantial impact on the development of a promising epigenetic approach for investigating targeted therapies for MM with high SRSF1 expression.
2022-09-04 | GSE160724 | GEO