Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients

Abstract

Abstract. Peroxiredoxins (Prdxs) are a family of antioxidant enzymes that are also known as scavengers of peroxide in mammalian cells. Some reports have shown that the overexpression of Prdx1, which is one of the peroxiredoxins that is a ubiquitously expressed protein, was related to a poor prognosis in several types of human cancers. In this study, we investigated the expression levels of Prdx1 in esophageal squamous cell carcinoma by immunohistochemistry, and the correlation between the Prdx1 expression and the clinical status was elucidated. Immunohistochemical staining was performed in 114 samples which were collected from surgical esophageal cancer specimens. Cytoplasmic staining of Prdx1 was evaluated based on the following scoring criteria: Grade I, negative or weak staining; Grade II, moderate staining; and Grade III, strong staining. The percentage of patients with a Grade I expression of Prx1 was 20% (23 of 114), 44% had Grade II (50 of 114), and 36% had Grade III (41 of 114). The Prdx1 immunoreactivity showed an inverse significant correlation with T-category (P<0.0001), lymph node metastasis (P=0.048), and stage (P=0.001). In addition, the patients with tumors exhibiting a reduced Prdx1 expression had shorter overall survival (P=0.022) in comparison to the patients with tumors which had a higher Prdx1 expression. Currently, Prdx1 has been shown to act as a tumor suppressor. Our results provide strong evidence that the reduced Prdx1 expression is an important factor in esophageal squamous cancer progression and could serve as a useful prognostic marker. IntroductionEsophageal cancer is the eighth most frequent cancer and the sixth most frequent cause of death from malignant disease in the world (1). Esophageal squamous cell carcinoma (ESCC) is the most common type in Japan (2). A large number of reports about genetic changes in ESCC have already been published, but little is known about the major tumor suppressor genes or major oncogenes in the process of tumor progression of this malignant disease. ESCC is still a fatal malignancy with a 5-year rate of 5% to 20% for advanced stage patients undergoing a curative resection (3). This miserable prognosis for ESCC involves not only the aggressive character of this tumor but also the limited number of useful markers available for diagnostic purposes.Therefore, better markers which indicate the malignant potential of ESCC should help in the prognosis or optimal treatment of the patients suffering from this disease. In this study, we focus on Prdx1, one of the peroxiredoxins (Prdxs) belonging to a novel antioxidant family, which has been reported to be a tumor suppressor gene. Prdx1 has been thought to have an inhibitory function for both c-Abl and c-Myc, of which active forms cause several neoplasms (4,5). Neumann et al (6) showed, using Prdx1 knockout mice, that Prdx1 expression correlated with the reactive oxygen species and the incidence of malignant disease. Moreover, our previous study using a cDNA microarray showed that one of the novel histone deacet...

Increasing discordant antioxidant protein levels and enzymatic activities contribute to increasing redox imbalance observed during human prostate cancer progression

“…In addition to scavenging free radicals and ROS through the conserved cysteine residues, these Prxs also participate in multiple cell-signaling pathways, including those involving tumor suppressor proteins [36]. Since evidence implicates Prx1 as a tumor suppressor and Prxs are known to scavenge excess ROS [37-38], sulfinylation of Prxs may indicate persistent oxidative stress in high grade PCa tissues, which may contribute to redox imbalance and promote PCa progression. It has been shown that Trx1 directly transnitrosylates peroxiredoxin 1 at Cys173 and Cys83 and protects it from H 2 O 2 -induced overoxidation [39], thus, increased amounts of PrxSO3 could possibly be due to the presence of oxidized Trx1 (non-functional form), which cannot reduce PrxsSO3 back to active enzymes.…”

RBMS3 at 3p24 Inhibits Nasopharyngeal Carcinoma Development via Inhibiting Cell Proliferation, Angiogenesis, and Inducing Apoptosis

“…Notably, the apoptotic index between RBMS3 transfected NPC cells and control cells showed significant difference after STS treatment, indicating a unique mechanism underlying the strong pro-apoptotic effect of RBMS3 in NPC cancer cells. It has been reported that RBMS3 increased the expression of Prx1 transcription factor [19], which is a tumor suppressor in esophageal squamous cell carcinoma [24]. Prx1, as a novel interaction partner for the lifespan regulator protein p66Shc, binds to the N-terminal domain of p66Shc [25], [26], and subsequently induces changes in the permeability transition of mitochondrial membranes and results in the release of cytochrome C and apoptosome activation [27], [28].…”

Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

“…The outcome will depend on the balance of many molecular forces, pro and against, acting at the same time. At the end, many studies have suggested that Prx I plays a functional role in human carcinogenesis (28)(29)(30)(31)(32).…”