AKR1B1 and AKR1B10 as Potential Prognostic Biomarkers of Endometrial Cancer

Vollständiger Abstract

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Endometrial cancer (EC) is the most common gynecological malignancy with rising incidence, yet reliable non-invasive prognostic biomarkers for preoperative risk stratification and treatment guidance are needed. This pilot study investigated whether plasma levels of aldo-keto reductase family 1 member B1 (AKR1B1) and aldo-keto reductase family 1 member B10 (AKR1B10) could serve as non-invasive prognostic biomarkers in EC. Plasma samples were collected preoperatively from 78 postmenopausal women with histologically confirmed EC alongside clinicopathological data including histological grade, depth of myometrial invasion, lymphovascular invasion, and metastatic status. AKR1B1 and AKR1B10 protein levels were quantified using enzyme-linked immunosorbent assays (ELISAs) in 72 and 64 plasma samples, respectively, and data were analyzed using R v4.3.0. Plasma AKR1B10 levels were significantly higher in Grade 3 compared to Grade 1–2 EC patients; and should be considered with caution given the limited Grade 3 sample size. A model combining both AKR1B1 and AKR1B10 with clinical variables (BMI, age, smoking, parity, hormone replacement therapy, previous use of contraceptives) showed limited discriminative ability for preoperative lymphovascular invasion prediction and is not suitable for clinical use in its current form. Survival analysis revealed that patients with plasma levels of both AKR1B1 and AKR1B10 below the median showed significantly better overall (p = 0.04, hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.10–1.01) and recurrence-free survival (p = 0.005, HR = 0.09, 95% CI: 0.02–0.49) compared to the remainder of the cohort. These preliminary, hypothesis-generating findings suggest the potential of circulating AKR1B proteins as candidate prognostic biomarkers in EC, requiring prospective validation in larger cohorts.