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Article

GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients

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Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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Institute of Medical Statistics and Informatics, 11000 Belgrade, Serbia
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Institute of Medical Chemistry, 11000 Belgrade, Serbia
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Clinic for Gynecology and Obstetrics “Narodni front”, 11000 Belgrade, Serbia
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Clinic of Urology, Clinical Center of Serbia, 11000 Belgrade, Serbia
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Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(12), 2038; https://doi.org/10.3390/cancers11122038
Received: 19 November 2019 / Revised: 8 December 2019 / Accepted: 13 December 2019 / Published: 17 December 2019
(This article belongs to the Special Issue Renal Cell Carcinoma)
Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis. View Full-Text
Keywords: glutathione transferase omega 1; glutathione transferase omega 2; polymorphism; PI3K/Akt/mTOR; Raf/MEK/ERK; IL-1β; pro-IL-1β glutathione transferase omega 1; glutathione transferase omega 2; polymorphism; PI3K/Akt/mTOR; Raf/MEK/ERK; IL-1β; pro-IL-1β
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MDPI and ACS Style

Radic, T.; Coric, V.; Bukumiric, Z.; Pljesa-Ercegovac, M.; Djukic, T.; Avramovic, N.; Matic, M.; Mihailovic, S.; Dragicevic, D.; Dzamic, Z.; Simic, T.; Savic-Radojevic, A. GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients. Cancers 2019, 11, 2038. https://doi.org/10.3390/cancers11122038

AMA Style

Radic T, Coric V, Bukumiric Z, Pljesa-Ercegovac M, Djukic T, Avramovic N, Matic M, Mihailovic S, Dragicevic D, Dzamic Z, Simic T, Savic-Radojevic A. GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients. Cancers. 2019; 11(12):2038. https://doi.org/10.3390/cancers11122038

Chicago/Turabian Style

Radic, Tanja, Vesna Coric, Zoran Bukumiric, Marija Pljesa-Ercegovac, Tatjana Djukic, Natasa Avramovic, Marija Matic, Smiljana Mihailovic, Dejan Dragicevic, Zoran Dzamic, Tatjana Simic, and Ana Savic-Radojevic. 2019. "GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients" Cancers 11, no. 12: 2038. https://doi.org/10.3390/cancers11122038

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