Expression and prognostic significance of human peroxiredoxin isoforms in endometrial cancer

Abstract

Abstract. Endometrial cancer is a common type of malignant tumor of the human female genital tract, which typically occurs after menopause. Asian nations, including Korea, Japan and China, have a 4-5 times lower incidence than Western industrialized nations. However, in recent years, there has been a marked increase in the incidence of the disease. Peroxiredoxin (Prx) is an antioxidant enzyme that consists of six isoforms in mammals. These enzymes share a common reactive Cys residue in the N-terminal region, and are capable of breaking down H 2 O 2 as a peroxidase and involving thioredoxin or glutathione as the electron donor. In the present study, we evaluated the expression of Prx isoforms in normal endometrium, endometrial hyperplasia and endometrial cancer. A total of 240 patients, diagnosed with endometrial cancer by immunohistochemistry, were enrolled in this study. Results showed that Prx I, III, IV and V were negative or weakly expressed in normal endometrium, whereas levels of Prx II and VI were strongly expressed. Notably, the expression levels of Prx III and V were upregulated in endometrial cancer, compared with normal endometrium and endometrial hyperplasia. However, no differences in the staining intensities according to the grade of lesion were observed in the other Prx isoforms. The Kaplan-Meier survival analysis demonstrated that Prx V expression in endometrial cancer is significantly associated with survival rate. Therefore, we suggest that Prx V is a clinically significant prognostic marker for the development of endometrial cancer. IntroductionEndometrial cancer is the most frequent gynecological malignancy in the world (1). Endometrial adenocarcinoma is the most common type of diagnosed endometrial cancer, which originates in glandular tissue and is characterized via a sequence of hyperplastic changes in the endometrium; each with increasing malignant potential. Endometrial adenocarcinoma is graded histologically according to the International Federation of Gynecology and Obstetrics. In this system, grade 1 designates a well-differentiated tumor with a <5% solid growth pattern, grade 2 designates a moderately differentiated tumor of 5-50% solid growth, and grade 3 designates a poorly differentiated tumor with >50% solid tumor. Peroxiredoxins (Prxs), synonymous with thioredoxin peroxidases, are a family of proteins, whose members were initially identified as thiol-specific antioxidant enzymes (2-4). Prxs are involved in the enzymatic degradation of hydrogen peroxide, organic hydroperoxides and peroxynitrite (5-7). They are found in a wide range of organisms, including bacteria, plants and mammals, and are classified into three major subclasses: typical 2-cysteine Prxs (Prx I-IV), atypical 2-cysteine Prxs (Prx V) and 1-cysteine Prxs (Prx VI). A number of studies have reported Prx overexpression in various types of malignant cancer cells (8,9). Therefore, we investigated the Prx isoforms (Prx I-IV) to determine whether their expression is associated with cancer progression in endometrial cancer...

Overexpression of peroxiredoxin-3 and -5 is a potential biomarker for prognosis in endometrial cancer

“…proteins were compared between endometrial cancer and paired normal endometrial tissues using immunohistochemistry. Based on the RT-PCR analysis, which detected marked changes in the expression of PRDX1, PRDX3, and PRDX6 mRNAs, and a previous study in which PRDX5 was found to be overexpressed in endometrial cancer (27), immunohistochemical staining for PRDX1, PRDX3, PRDX5, and PRDX6 was performed. The results showed that 59.5% of endometrial cancer samples and 31.6% of normal endometrial samples showed strong cytoplasmic staining for PRDX3, and statistical analysis revealed that PRDX3 was significantly overexpressed in endometrial cancer compared with normal endometrial tissue (P=0.0001; Table II; Fig.…”

Expression and function of peroxiredoxins in gynecological malignancies

“…Han et al (64) showed that the expression levels of peroxiredoxin 3 and 5 were elevated in endometrial cancer as compared to normal endometrium and endometrial hyperplasia, which supported that peroxiredoxin 3 and 5 might be involved in the development of endometrial cancer and serve as tumor markers to predict the progression of endometrial cancer. In addition, they then confirmed that a high expression of peroxiredoxin 5 in endometrial cancer, but not other isoforms, was significantly associated with a worse survival rate, suggesting that peroxiredoxin 5 may be a potential prognostic biomarker for endometrial cancer.…”

Peroxiredoxins and the Regulation of Cell Death

“…Increased Prx3 expression is reported in breast and lung carcinomas ( Noh et al, 2001 ; Park et al, 2006 ), prostate ( Whitaker et al, 2013 ), ovarian ( Wang et al, 2013 ), cervical ( Hu et al, 2013 ), endometrial ( Han et al, 2012 ), mesothelioma ( Kinnula et al, 2002 ) and hepatocellular carcinomas ( Choi et al, 2002 ). Also, the developmental abnormalities and malignancies associated with Fanconi anemia in humans has also been closely linked to deregulation of Prx3 function ( Mukhopadhyay et al, 2006 ).…”