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In this study, we aimed to leverage publicly available datasets to identify EBV\u2013host gene interactions and re-map their expression at single-cell resolution. We conducted a meta-analysis to identify differentially expressed genes, mapped these genes to EBV\u2013host interaction data, constructed a network, and performed pathway enrichment. Single-cell RNA sequencing datasets were used to map these genes at cellular resolution. We analysed differences in cell cycle, immune signaling, cell\u2013cell interactions, and assessed prognostic associations of UPS signature using the GEPIA2 platform. We identified 85 EBV-interacting DEGs regulated by lytic-phase proteins. Clustering highlighted genes related to the ubiquitin\u2013proteasome system (UPS). Single-cell analyses confirmed elevated UPS-related gene expression in NPC. UPS-High cells exhibited lower proliferative activity, enriched stemness signaling, and reduced antigen presentation and immune activation, whereas UPS-Low cells showed marked upregulation of growth-promoting pathways. High UPS expression was associated with poorer outcomes in pan-cancer, head and neck squamous cell carcinoma, and marginally significant in the small NPC datasets. The proportion of UPS-High cells varied widely across patients. UPS activity, influenced by EBV lytic proteins, is linked to immune evasion, stemness, proliferation, and adverse prognosis. These findings support UPS as a potential biomarker and therapeutic target in NPC, warranting validation and functional studies.<\/jats:p>","DOI":"10.1038\/s41598-025-34808-4","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T19:44:38Z","timestamp":1771962278000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The ubiquitin\u2013proteasome system is an important driver of EBV-associated nasopharyngeal carcinoma progression: a meta-analysis of transcriptomic data"],"prefix":"10.1038","volume":"16","author":[{"given":"Hana","family":"Ratnawati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ardo","family":"Sanjaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldrich","family":"Christiandy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence S.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Ott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"34808_CR1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.5732\/cjc.011.10328","volume":"31","author":"M Adham","year":"2012","unstructured":"Adham, M. et al. 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