淋巴细胞与单核细胞比值可预测生存，且与弥漫性大 B 细胞淋巴瘤中的 miR-222-3p 和 miR-26b-5p 存在表观遗传关联。

Lymphocyte to monocyte ratio predicts survival and is epigenetically linked to miR-222-3p and miR-26b-5p in diffuse large B cell lymphoma.

机构信息

Technology of Medical Laboratory Department, College of Applied Health Science Technology, Misr University for Science and Technology, 77, Almotamayez District, 6th October, Egypt.

Department of Histochemistry and Cell Biology, Medical Research Institute, Alexandria University, Alexandria, Egypt.

出版信息

Sci Rep. 2023 Mar 25;13(1):4899. doi: 10.1038/s41598-023-31700-x.

DOI:10.1038/s41598-023-31700-x

PMID:36966176

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10039925/

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. 10-20% of the patients present with bone marrow (BM) involvement which predicts a worse survival. This study aimed to determine the prognostic significance of serum miR-222-3p, miR-26b-5p, EBV-miR-BHRF1-2-5p, and EBV-miR-BHRF1-2-3p and correlate their levels to clinical and haematological markers in DLBCL with special emphasis on the lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio. We also studied the role of BM BMI1 and PIM2 proteins in predicting BM infiltration. Serum miRNAs were studied on 40 DLBCL and 18 normal individuals using qRT-PCR. BMI1 and PIM2 proteins were studied on BM biopsies by immunohistochemistry. The results were correlated with clinical and follow-up data. All the studied miRNAs were dysregulated in DLBCL serum samples. BMI1 and PIM2 were expressed in 67% and 77.5% of BM samples, respectively. LMR was significantly associated with disease-free survival (DFS) (P = 0.022), miR-222-3P (P = 0.043), and miR-26b-5p (P = 0.043). EBV-miR-BHRF1-2-3p was significantly correlated to haemoglobin level (P = 0.027). MiR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p expressions were significantly correlated to each other (P = 0.001). There was no significant correlation between the studied markers and follow-up data. LMR is a simple method for predicting survival in DLBCL. MiR-222-3p and miR-26b-5p may be implicated in an immunological mechanism affecting patients' immunity and accordingly influence LMR. The correlation between miR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p may indicate a common mechanism among the 3 miRNAs that may explain DLBCL pathogenesis.

摘要

弥漫性大 B 细胞淋巴瘤 (DLBCL) 是最常见的非霍奇金淋巴瘤类型。10-20%的患者存在骨髓 (BM) 受累，这预示着预后更差。本研究旨在确定血清 miR-222-3p、miR-26b-5p、EBV-miR-BHRF1-2-5p 和 EBV-miR-BHRF1-2-3p 的预后意义，并将其水平与 DLBCL 的临床和血液学标志物相关联，特别强调淋巴细胞-单核细胞比值 (LMR) 和中性粒细胞-单核细胞比值。我们还研究了 BM BMI1 和 PIM2 蛋白在预测 BM 浸润中的作用。使用 qRT-PCR 研究了 40 例 DLBCL 和 18 例正常人的血清 miRNA。通过免疫组织化学研究 BM 活检中的 BMI1 和 PIM2 蛋白。结果与临床和随访数据相关联。所有研究的 miRNA 在 DLBCL 血清样本中均失调。BMI1 和 PIM2 在 67%和 77.5%的 BM 样本中表达。LMR 与无病生存 (DFS) 显著相关 (P = 0.022)、miR-222-3P (P = 0.043) 和 miR-26b-5p (P = 0.043)。EBV-miR-BHRF1-2-3p 与血红蛋白水平显著相关 (P = 0.027)。miR-222-3p、miR-26b-5p 和 EBV-miR-BHRF1-2-5p 之间的表达呈显著相关性 (P = 0.001)。研究标记物与随访数据之间无显著相关性。LMR 是预测 DLBCL 生存的一种简单方法。miR-222-3p 和 miR-26b-5p 可能参与影响患者免疫的免疫机制，并因此影响 LMR。miR-222-3p、miR-26b-5p 和 EBV-miR-BHRF1-2-5p 之间的相关性可能表明这 3 个 miRNA 之间存在共同机制，该机制可能解释了 DLBCL 的发病机制。