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Sources of Funding: None

Introduction

γ-glutamyltransferase (GGT), which is expressed in various human cancer cells, is known as a membrane-bound enzyme playing a protective role from oxidative stress. Recent studies indicated that GGT can also exert pro-oxidant effects at the membrane surface and the extracellular microenvironment, contributing to the regulation of proliferative/apoptotic balance, the acquisition of chemo-resistance, and cancer progression. Here, we explored the prognostic role of serum GGT in advanced urothelial carcinoma (aUC) patients.

Methods

This retrospective study included 126 consecutive aUC patients (inoperable cT4 and/or metastases to lymph nodes/distant organs) treated at a single cancer center from 2004 to 2016. Of the 126 patients, 93 (74%) received systemic chemotherapy. Variables collected included age, gender, performance status (PS), body mass index (BMI), hydronephrosis, primary site, lymph node/visceral metastasis, prior curative surgery, therapies for aUC, hemoglobin, white blood cell count, creatinine, albumin, alkaline phosphatase, lactate dehydrogenase (LDH), corrected calcium, C-reactive protein (CRP), aspartate/alanine aminotransferase, and GGT. We assessed variables associated with overall survival (OS) using the Cox proportional hazards model.

Results

The median (range) serum GGT was 26 (7-252) U/L. During follow-up (median 12M), 92 patients died (2Y OS rate 24%). On multivariate analysis, GGT was an independent predictor for OS (HR 1.01 as a continuous variable, p = 0.007) along with age (HR 1.04, p = 0.003), BMI (HR 0.92, p = 0.005), visceral metastasis (HR 1.92, p = 0.006), albumin (HR 0.49, p = 0.032), log LDH (HR 2.63, p < 0.001), and log CRP (HR 1.41, p < 0.001). Next, the optimal cut-off of GGT was determined. When patients with GGT ≥43 U/L were defined as elevated, HR was highest on univariate Cox proportional hazards analysis (2.16). The 2Y OS rates for patients with elevated and non-elevated GGT were 5% and 30%, respectively (p < 0.001). The prognostic significance of elevated GGT was confirmed in multivariate analysis (HR 2.29, p = 0.001). Incorporation of GGT into the Bajorin&[prime]s model (PS and visceral metastasis) improved the c-index from 0.654 to 0.685.

Conclusions

This study is the first to demonstrate the prognostic significance of serum GGT in aUC patients.

Funding

None