Elevated UHRF1 predicts unfavorable clinical outcomes in adult T-cell leukemia/lymphoma: Clinicopathological analysis and preliminary in vitro observations

Background UHRF1 has been established as a susceptibility gene in multiple cancer types; however, its functional role in the pathogenesis of adult T-cell leukemia/lymphoma (ATLL) remains poorly defined. This study aimed to investigate UHRF1 expression in ATLL and assess its clinical and biological significance. Methods Immunohistochemistry was performed to evaluate UHRF1 protein expression in tumor tissues from 72 ATLL patients and 30 reactive lymphadenopathy controls. Univariate Cox’s proportional hazard regression model was used to screen the factors affecting OS and PFS, and multivariate Cox’s proportional hazard regression model was used to screen independent prognostic factors in ATLL. UHRF1 expression in the HuT-102 ATLL cell line and MT-4 cell line was evaluated by Western blotting and quantitative PCR, and shRNA-mediated knockdown was used to assess proliferation and apoptosis. Results UHRF1 protein was highly expressed in primary ATLL samples (P < 0.001, median 26.562 vs. 1.306), and the percentage of positive pixels (%Area) significantly higher than that in the control group (P < 0.001, median 9.914 vs. 0.574). Multivariate Cox regression analysis demonstrated that UHRF1 expression remained an independent prognostic predictor after adjustment for clinicopathological characteristics. For overall survival (OS): P = 0.026, HR = 2.397, 95%CI: 1.108–5.184; for progression-free survival (PFS): P = 0.042, HR = 1.959, 95%CI: 1.025–3.744. Mechanistically, UHRF1 knockdown significantly suppressed proliferation and induced apoptosis in ATLL cell lines (HuT-102 cells and MT-4 cell). Co-immunoprecipitation detected no stable interaction between UHRF1 and either AMPK or the PP2A catalytic subunit PPP2CA, and UHRF1 knockdown did not significantly alter LKB1, PPP2R4, or the p-AMPK (Thr172)/AMPK ratio; whether UHRF1 intersects with AMPK signaling remains to be determined. These findings identify UHRF1 as an independent adverse prognostic indicator in ATLL and provide preliminary biological evidence, though the underlying mechanisms require further validation in larger cohorts and in vivo models.