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

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.

Automated summary

The 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 in DLBCL and correlate their levels with clinical and haematological markers. The study also investigated the role of BM BMI1 and PIM2 proteins in predicting BM infiltration. It was found that all the studied miRNAs were dysregulated in DLBCL serum samples.