A Host miRNA Signature Correlates With Clinical Stage Across Epstein-Barr Virus-Associated Malignancies

Epstein-Barr virus (EBV) is a well-established oncogenic driver in several human cancers including diffuse large B-cell lymphoma (DLBCL) and nasopharyngeal carcinoma (NPC). Although viral miRNAs have been extensively explored as diagnostic tools, the clinical relevance of host miRNAs dysregulation across EBV-associated malignancies, particularly as a unified indicator of tumor progression, remains unclear. In this cross-sectional study, we analyzed plasma from 60 DLBCL patients and 233 NPC patients, along with matched tumor tissues from 20 NPC cases, and uncovered a consistent two-miRNA signature in circulation: hsa-miR-7-5p was progressively downregulated, while hsa-miR-210-3p was upregulated, in parallel with advancing clinical stage and metastatic burden. The inverse expression pattern was recapitulated in NPC tumor tissues by in situ hybridization, confirming its biological relevance at the lesion site. Notably, the association between this miRNA signature and disease severity was markedly more pronounced in EBV-positive tumors than in EBV-negative counterparts. Together, our data suggest that circulating hsa-miR-7-5p and hsa-miR-210-3p form a clinically informative, host-derived signature that tracks with tumor aggressiveness, and may offer a potential practical, non-invasive means to monitor disease progression of multiple EBV-associated cancers.