Veryaskina Yuliya A, Titov Sergei E, Skvortsova Natalia V, Kovynev Igor B, Antonenko Oksana V, Demakov Sergei A, Demenkov Pavel S, Pospelova Tatiana I, Ivanov Mikhail K, Zhimulev Igor F
Laboratory of Molecular Genetics, Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Laboratory of Gene Engineering, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Int J Mol Sci. 2024 Dec 13;25(24):13404. doi: 10.3390/ijms252413404.
Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics. The aim of the present study was to identify biomarkers with the potential to improve the accuracy of prognosis assessment in MM. Initially, miRNA sequencing was conducted on bone marrow (BM) samples from patients with MM. Subsequently, the expression levels of 27 microRNAs (miRNA) and the gene expression levels of ASF1B, CD82B, CRISP3, FN1, MEF2B, PD-L1, PPARγ, TERT, TIMP1, TOP2A, and TP53 were evaluated via real-time reverse transcription polymerase chain reaction in BM samples from patients with MM exhibiting favorable and unfavorable prognoses. Additionally, the analysis involved the bone marrow samples from patients undergoing examinations for non-cancerous blood diseases (NCBD). The findings indicate a statistically significant increase in the expression levels of miRNA-124, -138, -10a, -126, -143, -146b, -20a, -21, -29b, and let-7a and a decrease in the expression level of miRNA-96 in the MM group compared with NCBD ( < 0.05). No statistically significant differences were detected in the expression levels of the selected miRNAs between the unfavorable and favorable prognoses in MM groups. The expression levels of ASF1B, CD82B, and CRISP3 were significantly decreased, while those of FN1, MEF2B, PDL1, PPARγ, and TERT were significantly increased in the MM group compared to the NCBD group ( < 0.05). The MM group with a favorable prognosis demonstrated a statistically significant decline in TIMP1 expression and a significant increase in CD82B and CRISP3 expression compared to the MM group with an unfavorable prognosis ( < 0.05). From an empirical point of view, we have established that the complex biomarker encompassing the CRISP3/TIMP1 expression ratio holds promise as a prognostic marker in MM. From a fundamental point of view, we have demonstrated that the development of MM is rooted in a cascade of complex molecular pathways, demonstrating the interplay of genetic and epigenetic factors.
多发性骨髓瘤（MM）的特征是单克隆浆细胞不受控制地增殖，约占所有血液系统恶性肿瘤的10%。MM的临床结局可能表现出很大的变异性。MM的遗传和表观遗传特征的变异性无疑会影响肿瘤的动态变化。本研究的目的是确定有可能提高MM预后评估准确性的生物标志物。首先，对MM患者的骨髓（BM）样本进行了miRNA测序。随后，通过实时逆转录聚合酶链反应评估了27种微小RNA（miRNA）的表达水平以及ASF1B、CD82B、CRISP3、FN1、MEF2B、PD-L1、PPARγ、TERT、TIMP1、TOP2A和TP53在预后良好和不良的MM患者BM样本中的基因表达水平。此外，分析还涉及接受非癌性血液疾病（NCBD）检查患者的骨髓样本。研究结果表明，与NCBD组相比，MM组中miRNA-124、-138、-10a、-126、-143、-146b、-20a、-21、-29b和let-7a的表达水平有统计学意义的升高，而miRNA-96的表达水平降低（P<0.05）。MM组中预后不良和良好的患者之间，所选miRNA的表达水平未检测到统计学上的显著差异。与NCBD组相比，MM组中ASF1B、CD82B和CRISP3的表达水平显著降低，而FN1、MEF2B、PDL1、PPARγ和TERT的表达水平显著升高（P<0.05）。与预后不良的MM组相比，预后良好的MM组中TIMP1表达有统计学意义的下降，CD82B和CRISP3表达显著增加（P<0.05）。从经验角度来看，我们已经确定，包含CRISP3/TIMP1表达比值的复合生物标志物有望作为MM的预后标志物。从基础角度来看，我们已经证明，MM的发生源于一系列复杂的分子途径，表明了遗传和表观遗传因素之间的相互作用。
