Cross-Cohort Transcriptomic Analysis Links UBE2C to Endocrine Resistance in ER-Positive Breast Cancer
Hawrin Burhan Khudhur, Huda Jabbar Jawhar, Zhikal Omar Khudhur, Hardi Abdulqadir Hasan
Apex Medical Journal, 2026, Volume 1, Issue 1
Endocrine resistance is a major cause of treatment failure and recurrence in estrogen receptor-positive (ER+) breast cancer. Ubiquitin-conjugating enzyme E2C (UBE2C) is involved in cell division and may be associated with continued tumor growth during endocrine treatment. In this study, we examined UBE2C expression across four independent transcriptomic datasets representing experimental endocrine resistance, clinical treatment response, and long-term estrogen deprivation. In GSE10879, UBE2C expression was higher in long-term estrogen-deprived cells than in wild-type cells (Δlog2 = 0.713; Hedges’ g = 1.538; nominal P = 0.010; BH-FDR q = 0.060). In GSE10911, UBE2C expression was higher in all four resistant models, with the largest increase observed in anastrozole-resistant cells (Δlog2 = 0.376; Hedges’ g = 1.359; nominal P = 0.036; q = 0.108). In GSE20181, letrozole nonresponders showed a greater early increase in UBE2C than responders (Δlog2 = 0.329; Hedges’ g = 0.620; nominal P = 0.056; q = 0.112). After Benjamini-Hochberg correction across the six prespecified individual contrasts, no comparison remained significant at q < 0.05. An exploratory random-effects synthesis across three independent analytical contexts yielded an overall positive association (Hedges’ g = 0.777, 95% CI 0.323–1.231; P = 0.00079; I² = 0%); however, experimental resistance models and the clinical treatment-response cohort were interpreted separa