Downregulation of glutathione peroxidase 3 is associated with lymph node metastasis and prognosis in cervical cancer

Abstract

Abstract. Glutathione peroxidase 3 (GPX3) is a member of the glutathione peroxidase family of selenoproteins and is one of the key defensive enzymes against oxidative damages to host cells. Downregulation of GPX3 due to its promoter hypermethylation has been documented in several different types of cancer, indicating that GPX3 functions as a possible tumor suppressor. In the present study, we showed that GPX3 is also significantly downregulated in cervical cancer tissues compared to normal cervical tissues by qRT-PCR analyses and immunohistostainings. GPX3 expression was significantly related to lymph node metastasis and prognosis in cervical cancer patients. Treatment of cervical cancer cells with 5-aza-2'-deoxycytidine restored the expression of GPX3 and methylation-specific PCR (MSP) confirmed the CpG methylation of the GPX3 gene. Our results indicate that promoter methylation is one of the major causes of GPX3 downregulation in cervical cancer and GPX3 could serve as a predictive biomarker for lymph node metastasis and prognosis of cervical cancer.

GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome

“…Tumor suppressor function of GPX3 in vivo and in vitro has been identified in a number of tumors . Additionally, reduced expression of GPX3 caused by its promoter hypermethylation has been observed in various solid tumors . Simultaneously, our previous studies also have proved the epigenetic style of GPX3 in AML and chronic myeloid leukemia (CML), and further disclosed that hypermethylation of GPX3 promoter was a prognostically adverse indicator in AML .…”

“…have revealed that GPX3 plays a vital role in the competitiveness of leukemic stem cells (LSCs) and self‐renewal activity of HSCs . Recently, increasing studies have demonstrated the reduced expression of GPX3 and hypermethylation of GPX3 promoter in various types of malignancies . Furthermore, epigenetic mechanism regulating GPX3 expression was also identified in human cancer cells including esophageal squamous cell carcinoma (ESCC), cervical cancer (CC), gastric carcinoma (GC), and multiple myeloma (MM) .…”

Distinct prognostic values of mRNA expression of glutathione peroxidases in non–small cell lung cancer

“…However, patients with prostate cancer with high GPx2 expression on the biopsy specimen had significantly lower prostate-specific antigen (PSA), recurrence-free survival, and OS than those without any GPx2 expression 69. Downregulation of GPx3 significantly correlated with poor prognosis in hepatocellular carcinoma,70 cervical cancer,71 and gallbladder cancer 72. GPx3 is considered to be a novel tumor suppressor, because hypermethylation of the GPx3 promoter was detected in tumor samples from patients with Barrett’s esophagus35–37 as well as endometrial38 and prostate cancers,39 and downregulation of GPx3 was generally associated with a poor prognosis.…”

Promoter Methylation of Ezrin and its Impact on the Incidence and Prognosis of Cervical Cancer

“…For example, methylation of the ESR1 promoter was related to higher tumor grading of patients with CC [32]. CpG promoter methylation could result in GPX3 (a possible tumor suppressor) downregulation in CC [33]. The methylation of APC1A promoter was also closely correlated with biological features in CC and could therefore be used to predict poor prognosis of CC [34].…”