期刊
BRITISH JOURNAL OF CANCER
卷 124, 期 8, 页码 1428-1436出版社
SPRINGERNATURE
DOI: 10.1038/s41416-020-01237-1
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类别
资金
- Oncopeptides
- iCAN Digital Precision Cancer Medicine Flagship (Academy of Finland) [1320185]
- Cancer Society of Finland
- Sigrid Juselius Foundation
- University of Helsinki
- Helsinki University Central Hospital
This study evaluated the biological significance of esterase expression in multiple myeloma (MM) by analyzing gene expression profiling and genomic variants in patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). High or low expression of specific esterases in MM, such as UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4, and PON1, were significantly altered as patients progressed from NDMM to RRMM. Certain esterases, like OVCA2, PAFAH1B3, SIAE, USP4, and PCED1B, were identified as poor prognostic markers, suggesting their potential role in myeloma biology.
Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.
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