Expression of MicroRNA-155 and its associations with EBV serological markers and inflammatory cytokines in young lymphoma patients with evidence of active EBV infection

TL;DR

This study finds that miR-155 levels are higher in young lymphoma patients with active EBV infection and are linked to inflammatory markers like IL-32.

Contribution

The study identifies miR-155 as a potential non-invasive biomarker for EBV-related immune activation in young lymphoma patients.

Findings

Serum miR-155 levels were significantly higher in lymphoma patients compared to healthy controls.

miR-155 was strongly associated with EBV IgM positivity and inflammatory cytokines IL-18 and IL-32.

IL-32 positivity was a strong independent predictor of elevated miR-155 levels.

Abstract

The Epstein–Barr virus (EBV) is implicated in several lymphoproliferative disorders, particularly among children and adolescents who frequently experience primary EBV infection. MicroRNA-155 (miR-155), an oncogenic and immunoregulatory molecule, is known to participate in EBV-related immune modulation; however, its expression profile and relationship with EBV serological markers and inflammatory cytokines in young lymphoma patients remain insufficiently characterized. This cross-sectional observational study included 80 participants, comprising 40 young lymphoma patients with serological evidence of active EBV infection and 40 healthy controls. Serum EBV IgM and IgG levels were measured using ELISA, as were IL-18 and IL-32 concentrations, while serum miR-155 levels were quantified using qRT-PCR with an absolute quantification approach. The mean age of participants was 13.19 ± 2.51 years, and 55% were male. Serum miR-155 levels were significantly higher in lymphoma patients compared with controls (median: 1.13 vs. 0.43 ng/mL; p = 0.012). Elevated miR-155 expression was significantly associated with EBV IgM positivity (p < 0.001), IL-18 (p = 0.001), and IL-32 (p < 0.001). In multivariate logistic regression analysis, IL-32 positivity emerged as a strong independent predictor of elevated miR-155 levels (AOR = 19.02, p = 0.001). Receiver operating characteristic curve analysis demonstrated good discriminative performance of miR-155 (AUC = 0.87), with 87% sensitivity and 90% specificity at a cutoff value of ≥1.11 ng/mL. These findings indicate that serum miR-155 is significantly elevated in young lymphoma patients with serological evidence of active EBV infection and is statistically associated with inflammatory cytokines, particularly IL-32. miR-155 may represent a promising non-invasive biomarker reflecting EBV-related immune activation, although tissue-based EBV confirmation and mechanistic studies are required to establish causality.

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