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首页> 外文期刊>British Journal of Cancer >Prognostic significance of esterase gene expression in multiple myeloma
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Prognostic significance of esterase gene expression in multiple myeloma

机译：多发性骨髓瘤中酯酶基因表达的预后意义

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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.
机译：背景技术酯酶在底物特异性和生物学功能中不同，并且可以在癌症中显示出疑虑表达。该研究评估了多发性骨髓瘤（mm）中酯酶表达的生物学意义。分子医学研究所（FIMM）队列研究所基因表达分析和基因组变种评价，从新诊断为MM（NDMM）或复发/难治性mM（RRMM）的患者获得骨髓抽吸。 CD138 +血浆细胞富集并用于RNA测序和分析，并评估基因组变异。将MM的临床结果与遗传概况（Commpass）数据集进行个人评估的多发性骨髓瘤研究基础（MMRF）用于验证FIMM的发现。结果MM患者（NDMM，N？= 56; RRMM，N？=α78）提供171个骨髓抽吸物（NDMM，N？=？56; RRMM，N？=？115）。特定的酯酶以mm的毫米表现出相对高或低的表达，并且在NdMM至RRMM的进展上显着改变了特定酯酶（UCH15，SIAE，ESD，PAFAH1B3，PNPLA4和PON1）的表达。 OVCA2，PAFAH1B3，SIAE和USP4的高表达和PCED1B的低表达，被鉴定为差的预后标记物（P？＆amp; ＆amp; 0.05）。 MMRF Commpass DataSet提供了验证，验证PAFAH1B3和SIAE的表达，以及PCED1B的降低表达，预后不良。结论酯酶基因表达水平随着患者从NDMM到RRMM的进展而变化。高表达OVCA2，PAFAH1B3，USP4和SIAE，以及PCED1B的低表达，是MM的差的预后标志物，表明这些酯瘤在骨髓瘤生物学中的作用。

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