TY - JOUR
T1 - Impact of Serum γ-Glutamyltransferase on Overall Survival in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy
AU - Takemura, Kosuke
AU - Yuasa, Takeshi
AU - Inamura, Kentaro
AU - Amori, Gulanbar
AU - Koga, Fumitaka
AU - Board, Philip G.
AU - Yonese, Junji
N1 - Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown. Objective: The present study was designed to determine the prognostic role of serum GGT in patients with mRCC and the association between systemic and local GGT levels. Patients and Methods: Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with mRCC receiving tyrosine kinase inhibitor therapy. GGT expression was analyzed in 65 resected specimens using immunohistochemistry. Results: A total of 82 patients (56%) died during the follow-up period (median 34.9 months). Median OS was 16.0 months and 36.8 months in patients with elevated GGT levels and without elevated GGT, respectively (P < 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio [HR] 4.04, P < 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P < 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004). Conclusions: Elevated serum GGT was an unfavorable prognostic factor in mRCC, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.
AB - Background: γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown. Objective: The present study was designed to determine the prognostic role of serum GGT in patients with mRCC and the association between systemic and local GGT levels. Patients and Methods: Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with mRCC receiving tyrosine kinase inhibitor therapy. GGT expression was analyzed in 65 resected specimens using immunohistochemistry. Results: A total of 82 patients (56%) died during the follow-up period (median 34.9 months). Median OS was 16.0 months and 36.8 months in patients with elevated GGT levels and without elevated GGT, respectively (P < 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio [HR] 4.04, P < 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P < 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004). Conclusions: Elevated serum GGT was an unfavorable prognostic factor in mRCC, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.
UR - http://www.scopus.com/inward/record.url?scp=85085568966&partnerID=8YFLogxK
U2 - 10.1007/s11523-020-00719-9
DO - 10.1007/s11523-020-00719-9
M3 - Article
SN - 1776-2596
VL - 15
SP - 347
EP - 356
JO - Targeted Oncology
JF - Targeted Oncology
IS - 3
ER -