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Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
Published on: January 20, 2023
The expression of HSP70 and HSP90alpha in children with Wilms tumor
Yi Yang1, Zhi Bin Niu, Ying Hou
1Department of Pediatric Surgery, the Second Affiliated Hospital of China Medical University, Shenyang 110004, China.
Insights
Heat shock proteins (HSP70 and HSP90alpha) expression was lower in pediatric Wilms tumors but higher in survivors, suggesting their prognostic value in this childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Heat shock proteins (HSPs) are crucial in cellular stress responses and implicated in carcinogenesis.
- HSPs may serve as predictive markers for clinical outcomes in various cancers.
Purpose of the Study:
- To investigate the expression of Heat Shock Protein 70 (HSP70) and Heat Shock Protein 90alpha (HSP90alpha) in pediatric Wilms tumors.
- To explore the clinical significance and prognostic value of HSP70 and HSP90alpha in Wilms tumor patients.
Main Methods:
- Evaluated HSP70 and HSP90alpha expression in 30 Wilms tumor tissue samples using histochemistry and RT-PCR.
- Compared expression levels between tumor tissues and normal kidney controls.
- Correlated gene and protein expression with tumor histology, stage, and patient survival.
Main Results:
- HSP70 and HSP90alpha mRNA and protein levels were significantly lower in Wilms tumor tissues compared to normal kidney tissues.
- Expression was primarily localized to blastemal and epithelial components of the tumor.
- Higher HSP70 and HSP90alpha expression correlated with improved survival rates in pediatric patients.
Conclusions:
- HSP70 and HSP90alpha expression is reduced in Wilms tumors but shows a positive correlation with patient survival.
- These findings suggest that HSP70 and HSP90alpha may hold prognostic significance in pediatric Wilms tumor cases.
Background/Purpose:
Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. Some studies also showed that they might predict clinical prognosis. The aim of this study is to detect the expression of HSP70 and HSP90alpha in children with Wilms tumor and explore its clinical significance.
Methods:
The expression of HSP70 and HSP90alpha was evaluated in the tissue specimens of 30 patients (13 males and 17 females aged 5 months to 9 years with mean age of 37.4 +/- 23.9 months) with Wilms tumor by histochemistry and reverse transcriptase polymerase chain reaction techniques. According to the NWTS3 study criteria, all patients were favorable histological types, including mesenchymal type in 6, blastemal type in 12, and epithelium type in 7, and mixed type in 5. The clinical staging of the tumor included stage I in 4, stage II in 8, stage III in 12, and stage IV in 6.
Results:
On the reverse transcriptase polymerase chain reaction study, the amount of HSP70 and HSP90alpha mRNA in the tumor tissue was lower than in the controls. The HSP70 to beta-actin ratio was 0.74 +/- 0.14 and 1.38 +/- 0.22 in the tumor tissue and the normal kidney, respectively (P < .0001). The HSP90alpha to beta-actin ratio was 0.60 +/- 0.14 and 0.96 +/- 0.15 in the tumor tissue and the normal kidney, respectively (P < .0001). On immunolabeling, the expression of HSP70 and HSP90alpha was confined to blastemal and epithelial components, whereas the tumor stroma was negative. The expression of HSP70 and HSP90alpha was mainly located in the cytoplasm of the tubular epithelial cell, mesangial cell, and endothelial cell in the normal kidney. The positive expression rates of HSP70 and HSP90alpha proteins were significantly lower in the tumor group (73.3%, 22/30; 76.7%, 23/30) than in the control group (100%, 30/30; 100%, 30/30), P = .002 and P = 0.005, respectively. Positive correlation was found between HSP70 gene and protein expression (r = 0.64, P < .0001). Positive correlation was also found between HSP90alpha gene and protein expression (r = 0.67, P < .0001). HSP70 and HSP90alpha gene and protein expression showed no correlation with its corresponding tumor stages (P > .05). The expression of HSP70 and HSP90alpha genes was significantly higher in children who survived when compared with those patients who died during the follow-up period, P = .017 and P = 0.004, respectively. The positive expression rates of HSP70 and HSP90alpha proteins were also significantly higher in children who survived (82.6%, 19/23; 87.0%, 20/23) than in those who died (42.9%, 3/7; 42.9%, 3/7), P = .037 and P = 0.016, respectively.
Conclusions:
The expression of HSP70 and HSP90alpha decreased in Wilms tumor and is confined to blastemal and epithelial components; it was higher in patients who survived, which suggested that they might be of prognostic value.
