ArticleFrontiers in oncology2026
Clinicopathological significance and exploratory prognostic modeling of USP18 and YBX3 expression in clear cell renal cell carcinoma: a retrospective Chinese cohort study.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is clinically heterogeneous, and tissue biomarkers may complement conventional pathological risk assessment. Ubiquitin-specific protease 18 (USP18) and Y-box binding protein 3 (YBX3) have been implicated in tumor progression, but their clinicopathological and prognostic relevance in ccRCC remains uncertain. Methods: We retrospectively evaluated 98 patients with pathologically confirmed ccRCC using paired tumor-adjacent immunohistochemistry, clinicopathological correlation, Kaplan-Meier analysis, Cox regression, and exploratory receiver operating characteristic modeling. Immunohistochemical scores were analyzed continuously as the primary analytical scale; a cohort-median cutoff of ≥6 was used only for descriptive and exploratory survival stratification. Results: USP18 and YBX3 scores were higher in tumor than paired adjacent renal tissue (both p < 0.001) and were moderately correlated (Spearman rho = 0.540, p < 0.001). USP18-high expression was not associated with most clinicopathological variables and was not significant in categorical univariable survival analysis (HR 3.59, 95% CI 0.71-18.28; p = 0.124). YBX3-high expression was associated with inferior overall survival by the log-rank test (p = 0.047), while combined high expression showed exploratory survival separation (p = 0.019). Continuous USP18 and YBX3 scores were associated with mortality in univariable Cox models, but only 12 deaths occurred, precluding reliable multivariable biomarker validation or adequately powered interaction testing. Apparent in-sample AUC gains after adding biomarkers to clinical variables were small and unvalidated. Conclusion: USP18 and YBX3 are overexpressed and co-expressed in ccRCC. The evidence is stronger for YBX3 than for categorical USP18 expression, and the combined signal should be regarded as hypothesis-generating rather than proof of synergy or independent prognostic utility. Larger externally validated cohorts with prespecified cutoffs are required.
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