Plasma Glutathione S -Transferase P1-1 as a Prognostic Factor in Patients with Advanced Non-Hodgkin’s Lymphoma (Stages III and IV)

Abstract

Purpose: This study aims to investigate whether the plasma level of glutathione S-transferase P1-1 (GSTP1-1), which is a phase II detoxifying enzyme known to be a resistance factor for anticancer drugs, could be a prognostic factor of de novo non-Hodgkin lymphoma (NHL) in clinical stages (CSs) III and IV.Experimental Design: Study population consisted of 80 NHL patients with no prior treatment: 12 patients were at CS I, 14 at CS II, 25 at CS III, and 29 at CS IV. All 54 patients at CS III or CS IV were treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Plasma GSTP1-1 concentration was measured by ELISA. We stained lymph node tissues for GSTP1-1 using anti-GSTP1-1 monoclonal antibody 5F and quantitatively assessed the intensity of immunostaining by using the KS-400 image analyzing system.Results: There was a significant stepwise increment of plasma GSTP1-1 concentration from CS I to CS IV (P < 0.05). Of the 54 patients with CS III or IV treated with CHOP, 28 (52%) had elevated plasma GSTP1-1 levels. Plasma GSTP1-1 concentration tended to correlate with the intensity of GSTP1-1 expression in lymphoma tissues as assessed by immunostaining (P ‫؍‬ 0.07). The CR rates in patients at CS III and CS IV treated by CHOP, 55.2% (14 of 26) and 16.0% (5 of 28) for the low and high plasma GSTP1-1 groups, respectively, were significantly different (P < 0.01). For these two groups, the median survival times were 64 and 25 months, respectively (P < 0.01), and the median times to progression were 58 and 12 months, respectively (P < 0.01). There was no significant correlation between plasma GSTP1-1 concentrations and other NHL prognostic indicators in these patients as determined by univariate and multivariate analyses.Conclusion: These results showed that plasma GSTP1-1 is a useful prognostic factor for CS III and IV advanced NHL. Thus, it may be a promising strategy to treat NHL concomitantly with anticancer drugs and GSTP1-1-specific inhibitors.

Placental isoform glutathione S-transferase and P-glycoprotein expression in advanced nonsmall cell lung cancer

“…In neoplasms other than lung cancer, the overexpression of GST-pi and P-gp has been associated with decreased treatment response and survival. [16][17][18] In patients with lung cancer, the link between GST-pi and P-gp expression and tumor chemosensitivity has been documented by several trials in advanced NSCLC. 4,5,[7][8][9][10][11] In this regard, Hida et al observed that pretreatment serum GST-pi levels may be a useful parameter for predicting therapeutic response to combination chemotherapy regimens that include platinum compounds.…”

Glutathione S-transferase: differential expression of α, μ, and π isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma

“…GST enzymes have a broad substrate specificity [34] that includes substances with known mutagenic properties. Elevated serum GST p has been exploited as a serum tumor marker for gastrointestinal cancer [16] and more recently for non-Hodgkin lymphoma [35] as a method of predicting sensitivity to chemotherapy.…”

MRP1 and GSTp1 expression in non-small cell lung cancer does not correlate with clinicopathological parameters: A Slovakian population study

“…Wang et al (2011) confirmed that GSTp in comparison to MRP1 is the much more important mediator to predict the intrinsic resistance to cisplatin. The multivariate analysis showed that there was a significant correlation between increased plasma GSTp concentration and lower overall survival or progression-free survival Katahira et al (2004). This negative prognostic influence was strongest in stage I and II squamous cell lung carcinomas.…”