Preoperative Gamma-Glutamyltransferase Is Associated with Cancer-Specific Survival and Recurrence-Free Survival of Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus

Abstract

Introduction. To evaluate the prognostic significance of preoperative gamma-glutamyltransferase (GGT) on the subgroup of nonmetastatic renal cell carcinoma (RCC) with venous tumor thrombus. Materials and Methods. We retrospectively reviewed the institutional database and collected the medical data of 156 patients with nonmetastatic RCC with venous tumor thrombus between March 2004 and December 2014. Kaplan-Meier and Cox regression analyses were applied to determine the prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS). Results. The median value and optimal cutoff point of preoperative GGT were 23.0 and 37.5 IU/L, respectively. In the entire cohort, 67 (42.9%) patients experienced disease recurrence, and 46 (29.5%) patients died. Kaplan-Meier analysis revealed that the CSS and RFS rates were lower in patients with preoperative GGT ≥ 37.5 IU/L than in those with preoperative GGT < 37.5 IU/L. Multivariate Cox proportional hazard analysis demonstrated that high preoperative GGT was significantly associated with shorter CSS (hazard ratio [HR]: 2.115; 95% CI: 1.164–3.843; p = 0.014) and RFS (HR: 1.955; 95% CI: 1.166–3.276; p = 0.011), after adjusting other covariates. Conclusions. Preoperative GGT can serve as an independent prognostic biomarker of nonmetastatic RCC patients with venous tumor thrombus. Further prospective study is warranted to confirm our results.

Preoperative Albumin-Bilirubin Score for Postoperative Solitary Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh A Cirrhosis

“…Several studies have reported that GGT is involved in tumour development, progression, and chemotherapy resistance by releasing reactive oxygen species, controlling of CpG island methylation, inducing DNA damage and genome instability 21 - 23 . Clinical studies have shown that increased serum GGT levels are independently associated with the risk of several solid malignancies and always serve as an important prognostic marker for worse OS 24 - 25 . The predictive value of GGT for HCC patients was shown in cases that underwent hepatectomy and in cases with unresectable HCC that received TACE or chemotherapy 26 - 28 .…”

Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer

“…For example, nuclear factor-κB (NF-κB) is involved in inflammation-induced tumor growth [25]. The association of GGT with inflammation has been observed bidirectionally: elevated serum GGT can reflect inflammation-related oxidative stress [26], or can be a consequence of inflammatory cytokines such as tumor necrosis factor alpha [20].…”

“…Oxidative stress and inflammation are also pathways implicated in cancer development and progression, and positive GGT associations with risks of various cancer types have been demonstrated by several prospective studies [9][10][11][12]. Quite opposite to the abundance of cancer risk studies, relatively few studies have investigated the prognostic role of serum GGT in cancer outcomes: increased serum GGT has been inversely associated with survival in gastric cancer [13], colorectal cancer [14], ovarian cancer [15], breast cancer [16], endometrial cancer [17,18], cervical cancer [19], and renal cell carcinoma [20].…”

The prognostic significance of pretreatment serum γ-glutamyltranspeptidase in primary liver cancer: a meta-analysis and systematic review

“…Several potential mechanisms by which GGT affects tumor biology have been investigated. As a membrane-bound enzyme, GGT plays an essential role in maintaining the production of intracellular glutathione (GSH), which protects cells from reactive oxygen compounds and free radicals as a key antioxidant element [ 45 ]. Therefore, GGT may contribute to the formation of tumor microenvironment that protects tumor cells form oxidative stress and drug cytotoxic effects [ 46 , 47 ].…”