Citation: Kozlowski, M.; Michalczyk, K.; Witczak, G.; Kwiatkowski, S.; Mirecka, A.; Nowak, K.; Pius- Sadowska, E.; Machali ´ nski, B.; Cymbaluk-Ploska, A. Evaluation of Paraoxonase-1 and Pentraxin-3 in the Diagnosis and Prognosis of Endometrial Cancer. Antioxidants 2022, 11, 2024. https://doi.org/ 10.3390/antiox11102024 Academic Editors: Monica Emanuelli, Roberto Campagna and Gwonhwa Song Received: 13 September 2022 Accepted: 12 October 2022 Published: 13 October 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antioxidants Article Evaluation of Paraoxonase-1 and Pentraxin-3 in the Diagnosis and Prognosis of Endometrial Cancer Mateusz Kozlowski 1, *, Kaja Michalczyk 1 , Grzegorz Witczak 1 , Sebastian Kwiatkowski 2 , Aneta Mirecka 1 , Katarzyna Nowak 1 , Ewa Pius-Sadowska 3 , Boguslaw Machali ´ nski 3 and Aneta Cymbaluk-Ploska 1 1 Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, al. Powsta ´ nców Wielkopolskich 72, 70-111 Szczecin, Poland 2 Department of Obstetrics and Gynecology, Pomeranian Medical University in Szczecin, al. Powsta ´ nców Wielkopolskich 72, 70-111 Szczecin, Poland 3 Department of General Pathology, Pomeranian Medical University in Szczecin, al. Powsta ´ nców Wielkopolskich 72, 70-111 Szczecin, Poland * Correspondence: mateusz.kozlowski@pum.edu.pl Abstract: It is relevant to find new prognostic and diagnostic biomarkers for endometrial cancer. The study group consisted of 94 cases of endometrial cancer, the control group of 65 cases of normal endometrium. We evaluated PON1 and PTX3 serum levels. The ROC curve was plotted. The area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The Kaplan–Meier curve was used to assess survival. The cut-off level of PON1 was 142.6 ng/mL, with a sensitivity and specificity of 79 and 84% (p = 0.0321). The cut-off level of PTX3 was 4.2 ng/mL, with a sensitivity and specificity of 63 and 57% (p = 0.028). The favorable prognostic factor determined in serum was PON1 (for PFS: HR 0.93, 95% CI 0.86–1.03, p = 0.046; for OS: HR 0.96, 95% CI 0.89–1.08, p = 0.009). PON1 may be considered a potential biomarker in the diagnosis of endometrial cancer. Considering multivariate analysis, the PON1 serum level above the median is an independent favourable prognostic factor affecting PFS and OS. Considering Kaplan–Meier curves, longer recurrence-free survival and overall survival were found in patients with PON1 levels below the median. In view of the inconclusive results, we suggest that further studies should be conducted. Keywords: paraoxonase-1; pentraxin-3; PON1; PTX3; diagnostic marker; prognostic factor; endome- trial cancer 1. Introduction Endometrial cancer is recognized as one of the most common cancers in women. Its incidence is still increasing, not only in Western Europe but also in Central and Eastern Europe [1]. The pathogenesis of endometrial cancer is multifactorial, and known risk factors include age, race, metabolic syndrome, unopposed estrogen exposure and genetic predispositions [2]. However, it is important to note the significant role of oxidative stress in the development of many metabolic diseases. As it turns out, however, oxidative stress also plays a role in the carcinogenesis of many malignancies, which has been the subject of research for several years. Oxidation and reduction reactions lead to the formation of damaging molecules that affect cells. Imbalances between the production and accumulation of reactive metabolites and free radicals lead to oxidative stress. A key mechanism leading to oxidative damage is the hydroxyl radical. Other mechanisms that cause the modification of nucleic acids may be due to the action of lipid peroxidation products capable of forming adducts with DNA [3]. Oxidative stress leads to the adherence of monocytes to the vascular endothelium through the activation of lipid peroxidation products, which causes the syn- thesis of pro-inflammatory factors [4]. The expression of pentraxin-3 (PTX3) in endothelial cells can be regulated by a number of cytokines. PTX3 belongs to the pentraxin family, which is produced as response to inflammatory mediators and has numerous functions in Antioxidants 2022, 11, 2024. https://doi.org/10.3390/antiox11102024 https://www.mdpi.com/journal/antioxidants