Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Radic, Tanja, Coric, Vesna, Bukumiric, Zoran, Pljesa-Ercegovac, Marija, Djukic, Tatjana, Avramovic, Natasa, Matic, Marija, Mihailovic, Smiljana, Dragicevic, Dejan, Dzamic, Zoran, Simic, Tatjana, Savic-Radojevic, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966599/
https://www.ncbi.nlm.nih.gov/pubmed/31861116
http://dx.doi.org/10.3390/cancers11122038
_version_ 1783488773131075584
author Radic, Tanja
Coric, Vesna
Bukumiric, Zoran
Pljesa-Ercegovac, Marija
Djukic, Tatjana
Avramovic, Natasa
Matic, Marija
Mihailovic, Smiljana
Dragicevic, Dejan
Dzamic, Zoran
Simic, Tatjana
Savic-Radojevic, Ana
author_facet Radic, Tanja
Coric, Vesna
Bukumiric, Zoran
Pljesa-Ercegovac, Marija
Djukic, Tatjana
Avramovic, Natasa
Matic, Marija
Mihailovic, Smiljana
Dragicevic, Dejan
Dzamic, Zoran
Simic, Tatjana
Savic-Radojevic, Ana
author_sort Radic, Tanja
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6966599
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-69665992020-02-04 GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients Radic, Tanja Coric, Vesna Bukumiric, Zoran Pljesa-Ercegovac, Marija Djukic, Tatjana Avramovic, Natasa Matic, Marija Mihailovic, Smiljana Dragicevic, Dejan Dzamic, Zoran Simic, Tatjana Savic-Radojevic, Ana Cancers (Basel) Article 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. MDPI 2019-12-17 /pmc/articles/PMC6966599/ /pubmed/31861116 http://dx.doi.org/10.3390/cancers11122038 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Radic, Tanja
Coric, Vesna
Bukumiric, Zoran
Pljesa-Ercegovac, Marija
Djukic, Tatjana
Avramovic, Natasa
Matic, Marija
Mihailovic, Smiljana
Dragicevic, Dejan
Dzamic, Zoran
Simic, Tatjana
Savic-Radojevic, Ana
GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title_full GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title_fullStr GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title_full_unstemmed GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title_short GSTO1*CC Genotype (rs4925) Predicts Shorter Survival in Clear Cell Renal Cell Carcinoma Male Patients
title_sort gsto1*cc genotype (rs4925) predicts shorter survival in clear cell renal cell carcinoma male patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966599/
https://www.ncbi.nlm.nih.gov/pubmed/31861116
http://dx.doi.org/10.3390/cancers11122038
work_keys_str_mv AT radictanja gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT coricvesna gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT bukumiriczoran gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT pljesaercegovacmarija gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT djukictatjana gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT avramovicnatasa gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT maticmarija gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT mihailovicsmiljana gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT dragicevicdejan gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT dzamiczoran gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT simictatjana gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients
AT savicradojevicana gsto1ccgenotypers4925predictsshortersurvivalinclearcellrenalcellcarcinomamalepatients