Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma

Abstract

Background:Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC).Methods:Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months.Results:Median pretherapeutic serum GGT level was 25 U l−1. Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l−1 was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l−1), normal high (17.5 to <34.5 U l−1), elevated (34.5 to <181.5 U l−1), and highly elevated (⩾181.5 U l−1). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit.Conclusions:Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

Preoperative serum-gamma-glutamyltransferase (GGT) does not represent an independent prognostic factor in a European cohort of patients with non-metastatic renal cell carcinoma

“…Finally, we divided the patients into the four risk categories recently published by another study 20. For all three tested end points, we obtained no statistically significant differences in any of the four groups (p>0.05, for all pairwise logrank test comparisons).…”

“…The detailed functional mechanisms through which GGT impacts cancer biology, are still relatively poorly understood, especially since on the one hand GGT represents a sensitive indicator of hepatobiliary disorder, but on the other hand it has also been found to act as an oxidative stress marker, being able to exert antioxidative, as well as pro-oxidative functions within the tumour microenvironment 12. Moreover, GGT expression patterns have been shown to vary significantly among different types of human cancers 19 20. Several studies initially focused on the possible relationship between GGT and the incidence of hepatocellular carcinoma 26 27.…”

“…Patients’ clinical end points were calculated using the Kaplan-Meier method and compared by the logrank test. In order to validate the four risk categories recently published in another study (normal low (<17.5 UL(−1)), normal high (17.5–<34.5 UL(−1)), elevated (34.5–<181.5 UL(−1)) and highly elevated (⩾181.5 UL(−1)),20 we divided our cohort according to the GGT levels and performed pairwise log rank testing for each risk group. Multivariate Cox proportion analysis was performed to determine the influence of well-established clinicopathological factors including gender, age at the date of surgery, pathological T-stage, tumour grade, histological TN, as well as the preoperative serum-GGT on CSS, MFS and OS.…”

“…In detail, elevated serum-GGT levels have been found to represent an independent prognostic predictor in several different human malignancies, such as ovarian cancer,17 oesophageal squamous cell carcinoma,18 as well as endometrial cancer 19. Very recently, preoperatively assessed serum-GGT has also been proposed as a potential prognostic factor in patients with RCC 20 21. Therefore, the aim of this study was to validate the preoperative serum-GGT levels as a potentially helpful prognostic biomarker in a large European cohort of patients with non-metastatic RCC.…”

Model Based on Alkaline Phosphatase and Gamma-Glutamyltransferase for Gallbladder Cancer Prognosis

“…In addition, ALP has also been included in the Chinese University Prognostic Index, an liver cancer staging system that assigns a score of 3 when ALP is >200 IU/L (Leung et al, 2002). On the other hand, GGT was also recognized as a novel adverse prognostic marker in renal cancer, colorectal cancer, esophageal cancer, liver cancer and cholangiocarcinoma (He et al, 2013;Hofbauer et al, 2014;Ma et al, 2014;Yang et al, 2014). These previous studies strongly indicated the valuable prognostic roles of ALP and GGT in malignant tumors.…”