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Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma

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Abstract

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.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Dr. Hirofumi Hamano at the Department of Pharmacy, Okayama University Hospital, Japan for hel** with the analyses using bioinformatic data and the members of the Department of Urology at Okayama University Hospital, Japan, for their assistance in collecting patient samples and information. We would also like to thank the Central Research Laboratory, Okayama University Medical School, Japan, for providing analytical instruments, and Editage (ww.editage.jp) for English language editing.

Funding

This work was supported by the JSPS KAKENHI (Grant-in-Aid for Young Scientists, Grant number 20K16043) and the Research Foundation of Pharmaceutical Science.

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Authors and Affiliations

  1. Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-Ku, Okayama, 700-8558, Japan

    Jun Matsumoto, Anzu Nishimoto & Noritaka Ariyoshi

  2. Department of Urology, National Hospital Organization Okayama Medical Center, 1711-1 Tamasu, Kita-Ku, Okayama, 701-1192, Japan

    Shogo Watari

  3. Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-Ku, Okayama, 700-8558, Japan

    Hideo Ueki, Motoo Araki & Yasutomo Nasu

  4. Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata, Kita-Ku, Okayama, 700-8558, Japan

    Shoya Shiromizu, Naohiro Iwata, Tatsuaki Takeda, Soichiro Ushio, Makoto Kajizono & Yoshito Zamami

  5. Department of Pharmacy, Tottori University Hospital, 36-1 Nishi, Yonago, Tottori, 683-8504, Japan

    Masachika Fujiyoshi

  6. Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-Ku, Okayama, 700-8558, Japan

    Toshihiro Koyama

  7. Department of Urology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan

    Koichiro Wada

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  1. Jun Matsumoto
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Contributions

JM: Conceptualization, methodology, data curation, writing—original draft, and funding acquisition. AN: Formal analysis and data curation. SW and HU: Investigation and resources. SS and NI: writing—review & editing. TT, SU, MK, MF, TK, MA, YZ, and NA: writing—review & editing and supervision. KW: Investigation, writing—review & editing, and supervision. YN: Resources, writing—review & editing, and supervision. All authors have read and approved the final article.

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Correspondence to Jun Matsumoto.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences of Okayama University Hospital, Japan (February 14, 2018/No. 1802–033).

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Matsumoto, J., Nishimoto, A., Watari, S. et al. Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma. Mol Cell Biochem 478, 1779–1790 (2023). https://doi.org/10.1007/s11010-022-04637-4

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