LAUSR

Introduction: Uterine corpus endometrial carcinoma (UCEC) is one of the most commonly diagnosed cancers in women in the United States, where the death rate continues to climb by 1.9% every year due to poor prognostic and therapeutic methodologies. Recently, altered expression patterns of peroxiredoxins (PRDX) (1-6), a family of antioxidant enzymes comprised of six known isoforms, has been connected to overall outcome in many cancers. While recent studies have begun to unravel the potential of PRDXs as prognostic biomarkers in other cancers, PRDX expression patterns and their use as prognostic biomarkers in UCEC have yet to be explored. This study aimed to determine the value of PRDX1-6 as potential prognostic biomarkers for UCEC patients. Methods: To determine the impacts of PRDX1-6 expression on overall survival (OS) and relapse-free survival (RFS), UCEC samples (n=543) from the TCGA database available on the Pan-Cancer RNA seq platform on Kaplan-Meier Plotter (KM plotter) were utilized. The patient cohort was split into groups according to high PRDX expression status and low PRDX expression status using the autoselect best cutoff function in KM plotter where all possible cutoff values between the lower and upper quartiles of PRDX expression were computed. The best-performing threshold was used as the cutoff and data was plotted in a Kaplan-Meier plot. Hazard ratio (HR), 95% confidence interval (95% CI), and log-rank P value were calculated using the KM plotter platform. For molecular analyses, a total of 507 UCEC samples obtained from the PanCancer Atlas on the cBioportal platform were analyzed for PRDX1-6 copy number alterations (CNAs), and mRNA expression Z-scores relative to all samples were used to evaluate the association between CNAs and transcriptional levels of PRDXs. Results: Favorable OS associated with high PRDX2 (P=0.044, HR=0.65, 95% CI: 0.43-0.99) and high PRDX4 (P=0.01, HR=0.56, 95% CI: 0.36-0.88) mRNA levels. High PRDX2 (P=0.029, HR=0.56, 95% CI: 0.33-0.95) and high PRDX3 (P=0.034, HR=0.56, 95% CI: 0.33-0.96) expression in UCEC tumor samples correlated with favorable RFS. Shallow deletions were identified in PRDX2 (9.8%), PRDX3 (9.6%), and PRDX4 (14%) of the UCEC samples analyzed in cBioportal. Compared to diploid cells, shallow deletions in PRDX2 and PRDX3 correlated with decreased PRDX2 (P=1.33 × 10−12) and PRDX3 (P=8.17 × 10−13) mRNA levels, respectively. High expression of PRDX6 correlated with unfavorable OS (P=0.0021, HR=1.9, 95% CI: 1.25-2.88) and unfavorable RFS (P= 4.3 × 10−5, HR=2.88, 95% CI: 1.69-4.88). Notably, 41.2% of UCEC patients displayed PRDX6 copy number gain that correlated with increased PRDX6 mRNA levels (P= 8.69 × 10−24) compared to diploid cells. Conclusion: High PRDX2, PRDX3, and PRDX4 expression could serve as favorable UCEC prognostic biomarkers, while high PRDX6 expression may be a novel unfavorable prognostic biomarker. Citation Format: Lauren Lambros, Vien Sturm, Calli A. Davison-Versagli. Evaluating peroxiredoxins 1-6 and their potential as prognostic biomarkers for uterine corpus endometrial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6223.