Molecular Signatures of Multiple Myeloma Progression through Single Cell RNA-Seq
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ABSTRACT:
PROVIDER: PRJNA487220 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7738580_1.fastq.gz | Fastqsanger.gz | |||
| SRR7738580_2.fastq.gz | Fastqsanger.gz | |||
| SRR7738590_1.fastq.gz | Fastqsanger.gz | |||
| SRR7738590_2.fastq.gz | Fastqsanger.gz | |||
| SRR7738600_1.fastq.gz | Fastqsanger.gz |
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Project description:miRNA expression signatures in multiple myeloma
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Project description:Multiple myeloma (MM) is a malignant plasma cell disorder with well-defined clonal genetic/cytogenetic abnormalities. However, cellular heterogeneity is a key factor in MM’s progression, therapeutic decision, and response to treatment. Single cell whole transcriptome profiling (scRNA-Seq) offers an opportunity to dissect this molecular heterogeneity during MM progression to better understand the disease and guide rational therapy. Here, we examined 597 CD138 positive cells from 15 patients at different stages of MM progression using scRNA-Seq. We selected 790 genes based on a Coefficient of Variation (CV) approach which organized cells into four clusters (L1-L4) based on unsupervised clustering. Plasma cells from each patient contained a mixed population of plasma cells at different state of aggressiveness based on gene expression signature reflecting the inter-cellular heterogeneous nature of MM. Cells in the L1 group is characterized by low level expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathway having most cells from MGUS patients (p < 1.2x10-14). In contrast, low level of these genes in L1 group increased progressively and were the highest in the L4 group containing only cells from high-risk MM patients with t(4;14) translocations. Furthermore, 44 genes consistently overexpressed by pair-wised comparisons of the four groups strongly associated with a reduced overall survival in MM patients (APEX trial, p < 0.0001; Hazard Ratio (HR), 1.83; 95% CI, 1.33 to 2.52), particularly those in the bortezomib treated group (p < 0.0001; HR, 2.00; 95% CI, 1.39 to 2.89). No survival significance was observed for the dexamethasone treated group. Our study at the resolution of single cells showed that there is a mixed population of cells in each patient at different stages of MM progression and these cells can be organized into four different subgroups (L1 to L4). Consistent overexpression of the 44 genes from L1 to L4 groups is associated with patient outcome and treatment response. Our results show that oxidative phosphorylation, Myc target, and mTORC1 signaling genes are significant pathways for MM progression and affect MM prognosis and treatment stratification.
2018-11-17 | GSE118900 | GEO
Project description:Clonal Competition Assays Identify Fitness Signatures in Cancer Progression and Resistance in Multiple Myeloma
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Project description:The objective of this study is to identify genes involved in the pathogenesis of multiple myeloma (MM). In this study, we performed gene expression profiling of a total of 29 samples consisting of 19 clinical specimens, 7 myeloma cell lines and 3 normal samples. The microarray data were analysed by GeneSpring Software v14.9. A total of 5124 DEGs were identified in MM group vs control group (fold change≥2.0; P<0.05). Out of 5124 DEGs, 2696 and 2428 genes were up-regulated and down-regulated, respectively in MM group compared to the normal control group.
2022-07-20 | GSE72213 | GEO
Project description:Purpose Survival of patients with multiple myeloma is highly heterogeneous from periods of few weeks to more than ten years. We used gene-expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers. Methods In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival. A survival model was built from these genes. The validity of our model was assessed in our test set of 68 patients and in three independent cohorts comprising 853 multiple myeloma patients. Results The 15 strongest genes associated with the length of survival were used to calculate a risk score and to stratify patients in low-risk and high-risk. The survival-predictor score was significantly associated with survival in both the training and test sets and in the external validation cohorts. The Kaplan Meier estimates of rates of survival at 3 years were 90.5 percent (95 percent CI, 85.6 – 95.3), and 47.4 (95 percent CI, 33.5 - 60.1) respectively in our patients having a low-risk or high-risk, independently of traditional prognostic factors. High-risk patients constituted a homogeneous biological entity characterized by the overexpression of genes involved in cell cycle progression and its surveillance, while low-risk patients were heterogeneous and displayed hyperdiploid signatures. Conclusion Gene expression-based survival prediction and molecular features associated with high-risk patients may be useful for developing prognostic markers and may provide basis to treat these patients with new targeted anti-mitotics. Keywords: Gene-expression profiling
2008-08-05 | GSE7039 | GEO
Project description:In the present study, the gene expression profiling was carried out to identify the gene targets affected by miRNAs deregulated in multiple myeloma. A gene expression signature was generated for 45 patients of multiple myeloma as compared to controls (Pooled from 10 Hodgkin's disease samples).
2020-01-24 | GSE125361 | GEO
Project description:We used single cell RNA-Seq to examine molecular heterogeneity in multiple myeloma (MM) in 597 CD138 positive cells from bone marrow aspirates of 15 patients at different stages of disease progression. 790 genes were selected by coefficient of variation (CV) method and organized cells into four groups (L1-L4) using unsupervised clustering. Plasma cells from each patient clustered into at least two groups based on gene expression signature. The L1 group contained cells from all MGUS patients having the lowest expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathways (p < 1.2 × 10-14). In contrast, the expression level of these pathway genes increased progressively and were the highest in L4 group containing only cells from MM patients with t(4;14) translocations. A 44 genes signature of consistently overexpressed genes among the four groups was associated with poorer overall survival in MM patients (APEX trial, p < 0.0001; HR, 1.83; 95% CI, 1.33-2.52), particularly those treated with bortezomib (p < 0.0001; HR, 2.00; 95% CI, 1.39-2.89). Our study, using single cell RNA-Seq, identified the most significantly affected molecular pathways during MM progression and provided a novel signature predictive of patient prognosis and treatment stratification.
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