Abstract 6682: Circulating Epstein-Barr virus microRNAs associated with Hodgkin lymphoma prognosis

Abstract Background: Epstein-Barr virus (EBV) infection is an established causal factor for Hodgkin lymphoma (HL). MicroRNAs (miRNAs) are master regulators of gene expression and are ideal biomarkers. We profiled the circulating expression of 42 EBV miRNAs in HL patients to determine if EBV miRNA(s) can be a noninvasive biomarker for EBV+ HL or disease severity. Method: Plasma was obtained from 11 patients with HL in a tuberculosis and HIV-endemic setting in Cape Town, South Africa. EBV infection in HL tumor cells were confirmed using a clinical PCR assay. The expression of 42 miRNAs were measuring using a qPCR-based Mirxes ID3EALTM EBV miRNA panel. Wilcoxon test or Fisher’s test were used to compare data between two groups. Spearman’s rho was used for correlation analysis. Fold changes were calculated using the 2^-ΔΔCT method. Results: EBV+ HL patients were significantly older (p=0.04; Table 1). No miRNA was associated with EBV or prognostic factors at FDR<0.05. Of interest, miR-BART20-3p expression was 33% lower in EBV+ patients compared to EBV- patients (p=0.052) and did not correlate with age (rho=0.39, p=0.23). MiR-BART17-3p was inversely correlated with stage (rho=-0.61, p=0.047). MiR-BART2-5p correlated with International Prognostic Score (IPS; rho=0.72, p=0.01). miR-BART14-3p was inversely correlated with Eastern Cooperative Oncology Group (ECOG) score (rho=-0.60, p=0.049). MiR-BART11-5p and miR-BART14-5p were higher in patients that reported B-symptoms (11.2-fold p=0.01 and 2.5-fold p=0.02, respectively). In contrast, MiR-BART14-3p and miR-BART17-3p were 33% and 41% lower in patients with B-symptoms (both p=0.03). No miRNA was associated with HIV. Conclusion: Circulating EBV miRNAs were associated with HL disease severity but not EBV status. Further investigations into these candidate miRNAs will increase our understanding of HL disease progression as well as explore the potential of these miRNAs as therapeutics or therapeutic targets. Table 1. Citation Format: Soo Mi Lee, Cristina S. Bogsan, Jason T. Howard, Abigail G. Wandoff, Meng-Xuan Wu, Estelle Verburgh, Maxine van der Schyff, Frank J. Slack, Yujing J. Heng, Katherine Antel. Circulating Epstein-Barr virus microRNAs associated with Hodgkin lymphoma prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6682.