TY - JOUR
T1 - Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma
AU - Matsumoto, Jun
AU - Nishimoto, Anzu
AU - Watari, Shogo
AU - Ueki, Hideo
AU - Shiromizu, Shoya
AU - Iwata, Naohiro
AU - Takeda, Tatsuaki
AU - Ushio, Soichiro
AU - Kajizono, Makoto
AU - Fujiyoshi, Masachika
AU - Koyama, Toshihiro
AU - Araki, Motoo
AU - Wada, Koichiro
AU - Zamami, Yoshito
AU - Nasu, Yasutomo
AU - Ariyoshi, Noritaka
N1 - Funding Information:
This work was supported by the JSPS KAKENHI (Grant-in-Aid for Young Scientists, Grant number 20K16043) and the Research Foundation of Pharmaceutical Science.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.
AB - UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC.
KW - Genetic variant
KW - Polymorphism
KW - Renal cell carcinoma
KW - Survival
KW - UDP-glucuronosyltransferase
UR - http://www.scopus.com/inward/record.url?scp=85144896105&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144896105&partnerID=8YFLogxK
U2 - 10.1007/s11010-022-04637-4
DO - 10.1007/s11010-022-04637-4
M3 - Article
C2 - 36571650
AN - SCOPUS:85144896105
SN - 0300-8177
JO - Enzymologia
JF - Enzymologia
ER -
