4.7 Article

RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma

期刊

JOURNAL OF PERSONALIZED MEDICINE
卷 11, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/jpm11100988

关键词

multiple myeloma; risk stratification; gene expression profiling; precision medicine

资金

  1. INCa (Institut National du Cancer) [PLBIO18-362 PIT-MM, PLBIO19-098 INCA_13832 FATidique]
  2. ANR (the French National Research Agency) under the Investissements davenir program [ANR-16-IDEX-0006]
  3. ANR [2017-CE15-002401]
  4. SIRIC Montpellier Cancer [INCa-DGOS-Inserm_12553]
  5. PCSI ITMO
  6. FFRMG
  7. lInstitut Universitaire de France
  8. Labex EpiGenMed
  9. [ANR-18-CE15-0010-01 PLASMADIFF-3D]

向作者/读者索取更多资源

This study developed a gene risk score based on RNA-seq data for predicting the prognosis of newly diagnosed multiple myeloma patients treated with high-dose Melphalan and autologous stem cell transplantation. The risk score was associated with specific MM somatic mutation profiles and responses to targeted treatment, suggesting a potential utility for precision medicine strategies in MM.
Multiple myeloma (MM) is the second most frequent hematological cancer and is characterized by the clonal proliferation of malignant plasma cells. Genome-wide expression profiling (GEP) analysis with DNA microarrays has emerged as a powerful tool for biomedical research, generating a huge amount of data. Microarray analyses have improved our understanding of MM disease and have led to important clinical applications. In MM, GEP has been used to stratify patients, define risk, identify therapeutic targets, predict treatment response, and understand drug resistance. In this study, we built a gene risk score for 267 genes using RNA-seq data that demonstrated a prognostic value in two independent cohorts (n = 674 and n = 76) of newly diagnosed MM patients treated with high-dose Melphalan and autologous stem cell transplantation. High-risk patients were associated with the expression of genes involved in several major pathways implicated in MM pathophysiology, including interferon response, cell proliferation, hypoxia, IL-6 signaling pathway, stem cell genes, MYC, and epigenetic deregulation. The RNA-seq-based risk score was correlated with specific MM somatic mutation profiles and responses to targeted treatment including EZH2, MELK, TOPK/PBK, and Aurora kinase inhibitors, outlining potential utility for precision medicine strategies in MM.

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