GSTP1-1 in Ovarian Cyst Fluid and Disease Outcome of Patients With Ovarian Cancer

Abstract

Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, ≥Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2176-81)

GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer

“…In line with the present study of BC, previous investigations of Hodgkin's lymphoma, ovarian cancer, colorectal cancer, and even BC have also found the same improved survival rates when lymph node status was associated with polymorphic forms of GSTT1, GSTM1, and GSTP1 (Khedhaier et al, 2003;Huang et al, 2003;Hohaus et al, 2005;DeMichele et al, 2005;Beeghly et al, 2006;Holley et al, 2006;Kweekel et al, 2008;Kolwijck et al, 2009;Jones et al, 2009;Khrunin et al, 2010).…”

Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines

“…Increased GSTP1 expression in ovarian tumours ( n =41), relative to unmatched healthy ovarian samples ( n =12) and benign tumours ( n =25) has been described in a small Chinese study ( Cheng et al , 2000 ) and, consistent with our findings, GSTP1 expression in ovarian cyst fluid has been correlated with higher relapse rates following platinum-based chemotherapy ( Boss et al , 2001 ). In similar studies, GSTP1 expression in ovarian cyst fluid correlated both with serum CA125 levels and reduced patient survival ( Kolwijck et al , 2009 ), while in a small series ( n =30) of matched first and second-look laparotomies, increased GSTP1 expression was associated with disease progression, assessed by both more frequent relapses and reduced survival ( Surowiak et al , 2005 ).…”

Genomic instability of gold nanoparticle treated human lung fibroblast cells

“…Erlin 2 (SPFH2) belongs to a family of prohibitin proteins on the endoplasmic reticulum that degrade IP3 receptions on the ER membrane [47], dysregulation of this protein could disrupt cellular signaling pathways. Glutathione S transferase P (GSTP1-1) is a detoxification enzyme that catalyzes the conjunction of various hydrophilic compounds and electrophilic compounds with glutathione [48]. Ribonuclease inhibitor (RNH) in tissues has strong affinity binding to ribonucleases and recent studies show that it may have anti-tumor effects in hematopoietic cells [49].…”