Background/Objectives: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) based on differences in both genetic and epigenetic factors contributes to the dynamics of tumor growth and efficacy of cytoreductive therapy, as well as considerably affecting disease prognosis. This study aimed to detect microRNAs (miRNAs) capable of improving prognostic accuracy in DLBCL patients.Methods: We performed miRNA sequencing in bone marrow (BM) samples collected from DLBCL patients. Next, the expression levels of miRNAs in lymph node (LN) samples (n= 43) and BM samples (n= 70) were analyzed by real-time RT-PCR in the group of DLBCL patients.Results: It was found that the expression levels of miRNA-10b, -100, -125a, -125b, -126, -143, -23a and let-7a were statistically significantly reduced in the group of DLBCL patients who had a poor prognosis compared to DLBCL patients with a favorable prognosis (p< 0.05). Kaplan–Meier survival analysis demonstrated that the upregulated expression of miRNA-23a, miRNA-125a, and miRNA-100 was associated with better overall survival in DLBCL patients. A statistically significant elevation in the expression levels of miRNA-151a, miRNA-148b and miRNA-192 in the BM samples was observed for DLBCL patients both with and without BM involvement compared to BM samples from non-cancerous blood disease (NCBD) patients (p< 0.05). Statistically significant upregulation ofPD-L1,TIMP1,TOP2A, andTP53was observed in BM samples from DLBCL patients with and without BM involvement in comparison with BM samples from NCBD patients (p< 0.05).Conclusions: miRNA-23a, miRNA-125a, and miRNA-100 were shown to be potential prognostically significant biomarkers in DLBCL patients. Changes in expression levels of miRNA-151a, miRNA-148b, miRNA-192,PD-L1,TIMP1,TOP2A, andTP53reflect alterations in the BM without morphological or immunophenotypic signs of a DLBCL-related BM pathology.
背景/目的：弥漫性大B细胞淋巴瘤（DLBCL）的异质性源于遗传和表观遗传因素的差异，这种异质性影响肿瘤生长动态、细胞减灭治疗的疗效，并对疾病预后产生显著影响。本研究旨在探索能够提高DLBCL患者预后准确性的微小RNA（miRNA）。方法：我们对DLBCL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（RT-PCR）分析了DLBCL患者组中淋巴结（LN）样本（n=43）和BM样本（n=70）的miRNA表达水平。结果：研究发现，与预后良好的DLBCL患者相比，预后不良的DLBCL患者组中miRNA-10b、-100、-125a、-125b、-126、-143、-23a和let-7a的表达水平在统计学上显著降低（p<0.05）。Kaplan-Meier生存分析表明，miRNA-23a、miRNA-125a和miRNA-100的表达上调与DLBCL患者更好的总生存期相关。与非癌性血液疾病（NCBD）患者的BM样本相比，无论是否伴有BM受累，DLBCL患者的BM样本中均观察到miRNA-151a、miRNA-148b和miRNA-192的表达水平在统计学上显著升高（p<0.05）。与NCBD患者的BM样本相比，无论是否伴有BM受累，DLBCL患者的BM样本中均观察到PD-L1、TIMP1、TOP2A和TP53在统计学上显著上调（p<0.05）。结论：miRNA-23a、miRNA-125a和miRNA-100被证明是DLBCL患者中具有潜在预后意义的生物标志物。miRNA-151a、miRNA-148b、miRNA-192、PD-L1、TIMP1、TOP2A和TP53表达水平的变化反映了骨髓的改变，而这些改变并未伴随DLBCL相关骨髓病理的形态学或免疫表型迹象。
MicroRNAs in Diffuse Large B-Cell Lymphoma (DLBCL): Biomarkers with Prognostic Potential
肿瘤(癌症)患者之家