Takemura Kosuke, Yuasa Takeshi, Inamura Kentaro, Amori Gulanbar, Koga Fumitaka, Board Philip G, Yonese Junji
Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Target Oncol. 2020 Jun;15(3):347-356. doi: 10.1007/s11523-020-00719-9.
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.
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.
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.
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).
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.
γ-谷氨酰转移酶（GGT）是氧化应激的标志物。血清GGT升高与多种恶性肿瘤的不良生存相关；然而，关于转移性肾细胞癌（mRCC）尚无相关数据。此外，癌症组织中GGT的表达情况仍 largely未知。
本研究旨在确定血清GGT在mRCC患者中的预后作用以及全身和局部GGT水平之间的关联。
回顾性比较了146例接受酪氨酸激酶抑制剂治疗的连续性mRCC患者的治疗前血清GGT及其他临床病理参数与总生存期（OS）。采用免疫组织化学方法分析了65例切除标本中的GGT表达。
共有82例患者（56%）在随访期间死亡（中位时间34.9个月）。GGT水平升高和未升高的患者中位OS分别为16.0个月和36.8个月（P < 0.001）。多变量分析显示，血清GGT升高是独立的不良预后因素（风险比[HR] 4.04，P < 0.001），此外还有高中性粒细胞（HR 2.06，P = 0.041）、低白蛋白（HR 2.00，P = 0.006）、高乳酸脱氢酶（HR 2.68，P < 0.001）和高德瑞蒂斯比值（HR 1.97，P = 0.004）。肾癌细胞GGT表达呈阴性至弱阳性、中度和强阳性的患者术前血清GGT水平分别为29、48和109 U/l（P = 0.004）。
血清GGT升高是mRCC的不良预后因素，肾癌细胞中GGT的过表达可能是血清GGT升高的原因。
