RRC ID 62960
著者 Horie K, Kawakami K, Fujita Y, Matsuda Y, Arai T, Suzui N, Miyazaki T, Koie T, Mizutani K, Ito M.
タイトル Serum Exosomal Gamma-Glutamyltransferase Activity Increased in Patients with Renal Cell Carcinoma with Advanced Clinicopathological Features.
ジャーナル Oncology
Abstract BACKGROUND:There has been no clinically useful diagnostic or prognostic biomarker for renal cell carcinoma (RCC). Serum γ-glutamyltransferase (GGT) activity has been reported to be a prognostic marker for several types of cancer including RCC. Exosomes or small extracellular vesicles present in body fluids have potential as a biomarker. We have recently demonstrated that GGT activity on exosomes isolated from serum is useful for the differential diagnosis of prostate cancer and benign prostate hyperplasia. In this study, we aimed to examine if serum exosomal GGT activity could be a marker for RCC.
METHODS:We examined GGT1 expression and GGT activity in cell lysates and exosomes from culture medium of HK-2 proximal tubule epithelial and RCC cell lines. GGT activity was measured using a fluorescent probe for GGT, γ-glutamyl hydroxymethyl rhodamine green. Serum and serum exosomal GGT activities were measured in patients with RCC. GGT1 expression in RCC tissues was evaluated by immunohistochemical staining.
RESULTS:GGT1 levels in exosomes from KMRC-1, OS-RC-2 and 786-O cells were elevated compared with those from HK-2 cells. In exosomes, GGT1 expression correlated with GGT activity determined using a fluorescent probe for GGT. In RCC patients, serum exosomal GGT activity was elevated in those with advanced stages (III/IV vs. I/II, p = 0.037) and those with microvascular invasion (with vs. without, p = 0.034). Immunohistochemical analysis showed that membranous GGT1 expression was increased in RCC with microvascular invasion. Notably, preoperative serum exosomal GGT activity could predict the likelihood of having microvascular invasion diagnosed by pathological examination of surgically resected specimens.
CONCLUSIONS:Our results suggest that serum exosomal GGT activity could be a clinically useful marker for advanced clinicopathological features of RCC patients, and its combined use with conventional diagnostic modalities may improve the diagnosis and treatment of patients.
巻・号 98(10)
ページ 734-742
公開日 2020-1-1
DOI 10.1159/000508688
PII 000508688
PMID 32726790
MeSH Aged Carcinoma, Renal Cell / blood Carcinoma, Renal Cell / enzymology* Carcinoma, Renal Cell / pathology Cell Line, Tumor Exosomes / enzymology* Female Humans Immunohistochemistry Kidney Neoplasms / blood Kidney Neoplasms / enzymology* Kidney Neoplasms / pathology Male Middle Aged Neoplasm Metastasis Neoplasm Staging gamma-Glutamyltransferase / biosynthesis gamma-Glutamyltransferase / blood*
IF 2.642
リソース情報
ヒト・動物細胞 OS-RC-2(RCB0735)