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

Abstract

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.

Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma

“…With the development of clinical management of ccRCC, several prognostic factors, such as tumor grade and stage, tumor size, and tumor number, are well characterized. However, ccRCC has complex genetic and molecular alterations [24], which could affect the biological processes, and some of the biological processes are closely associated with the prognosis of ccRCC patients, such as autophagy [25], ferroptosis [15], and redox [26]. Most of these commonly used prognostic factors do not consider either genetic and molecular alterations or dysregulated biological processes, and it made these commonly used prognostic factors not perfect for accurate prognostic prediction of ccRCC patients [27].…”

Glutathione S‑transferase ω 1 promotes the proliferation, migration and invasion, and inhibits the apoptosis of non‑small cell lung cancer cells, via the JAK/STAT3 signaling pathway

“…Therefore, further investigations into the mechanism underlying NSCLC development and progression are essential for improving the treatment of NSCLC. The expression levels of GSTO1 were previously discovered to be upregulated in various types of cancer, including lymphoma, melanoma and colorectal cancer ( 7 , 16 , 21 ). However, to the best of our knowledge, the role of GSTO1 in NSCLC has not been investigated.…”

“…Chuang et al (14) illustrated that the expression levels of GSTO1 were upregulated in human bladder cancer cells. Moreover, GSTO1 has been revealed to contribute to cell growth, death, migration and invasion in several types of cancer cell (7,(15)(16)(17). For example, Wang et al (15) reported that GSTO1 was upregulated in cutaneous malignant melanoma (CMM) tissues and cells, where it contributed to CMM cell growth, migration and invasion.…”

Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

“…Cancer cells have altered lipid and amino acid metabolic pathways, glycolysis, and redox homeostasis [1,5]. Indeed, altered energy metabolism with upregulated glucose transporter expression, disrupted redox homeostasis with upregulated glutathione transferase (GST) and high telomerase activityare responses that maintain DNA integrity, retaining replication, proliferation and cancer cell resistance [1,5,6]. Chemotherapy has many disadvantages, including drug toxicity, rapid degradation, low specificity and limited targeting.…”