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Published on: October 10, 2020
Polymorphisms and Protein Expressions of Glutathione S-Transferase M1 and T1 in Non-Small Cell Lung Cancer
Murat Kiliç1, Ahmet Oğuz Ada2, Serpil Oğuztüzün3
1Ankara University, Vocational School of Health Services, Department of Pharmacy Services, Ankara, Turkey.
Objectives:
The deletion polymorphisms of glutathione S-transferase (GST) GSTM1 and GSTT1 genes result in the absence of the corresponding protein, which decreases the detoxification of carcinogens. Studies evaluating polymorphisms and protein expressions in the same patients are limited. Therefore, in this study, we aimed to investigate the association between polymorphisms and protein expressions of GSTM1 and GSTT1 in lung tissues of patients with non-small cell lung cancer (NSCLC).
Materials And Methods:
For protein expression and gene deletion studies, tumor and surrounding tumor free (normal) tissue of 33 patients with NSCLC were used. In paraffin-embedded tissues, immunohistochemistry was used to detect protein expressions, and multiplex polymerase chain reaction amplification was used to identify gene deletions.
Results:
GSTM1 and GSTT1 protein expressions were not detected in patients with GSTM1 and GSTT1 gene deletions, whereas protein expressions were detected in lung tissues of all patients carrying GSTM1 and GSTT1 genes. The protein expression level of GSTT1 was 2.0-fold higher in tumors of patients lacking GSTM1 genes than those with GSTM1 genes (p=0.018). Protein expression of GSTM1 was statistically higher in tumor tissues than in normal tissues of patients with GSTM1 genes (p=0.001).
Conclusion:
These results show that a) there is an association between gene deletions and protein expressions of GSTM1 and GSTT1 in patients with NSCLC, b) in the absence of GSTM1 genes, enhancement of expression of GSTT1 in tumors is likely to show that GSTT1 increases its capacity to detoxify the toxic electrophiles in tumors, and c) GSTM1 protein expression is higher in tumors compared with normal lung tissues of patients with NSCLC.
Insights
Glutathione S-transferase (GST) gene deletions, specifically GSTM1 and GSTT1, correlate with absent protein expression in non-small cell lung cancer patients. This suggests a link between genetic variations and protein function in carcinogen detoxification.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glutathione S-transferase (GST) genes, including GSTM1 and GSTT1, are crucial for detoxifying carcinogens.
- Gene deletion polymorphisms in GSTM1 and GSTT1 lead to absent protein, potentially impairing detoxification pathways.
- Limited studies have simultaneously assessed GST gene polymorphisms and their corresponding protein expression in lung cancer tissues.
Purpose of the Study:
- To investigate the association between GSTM1 and GSTT1 gene deletions and their protein expressions in non-small cell lung cancer (NSCLC) patient lung tissues.
- To understand how these genetic variations impact the functional capacity of GST enzymes in the context of lung cancer.
Main Methods:
- Utilized tumor and adjacent normal lung tissues from 33 NSCLC patients.
- Employed immunohistochemistry to detect GSTM1 and GSTT1 protein expression in paraffin-embedded tissues.
- Used multiplex polymerase chain reaction amplification to identify deletions in GSTM1 and GSTT1 genes.
Main Results:
- Absence of GSTM1 and GSTT1 protein expression was observed in patients with corresponding gene deletions.
- All patients with intact GSTM1 and GSTT1 genes showed detectable protein expression.
- GSTT1 protein expression was significantly higher (2.0-fold) in tumors lacking GSTM1 compared to those with GSTM1 (p=0.018).
- GSTM1 protein expression was significantly elevated in tumor tissues versus normal tissues from patients with GSTM1 genes (p=0.001).
Conclusions:
- Confirmed a significant association between GSTM1/GSTT1 gene deletions and their protein expression levels in NSCLC.
- Observed enhanced GSTT1 expression in tumors lacking GSTM1, suggesting a compensatory mechanism for detoxification.
- Demonstrated higher GSTM1 protein expression in NSCLC tumors compared to normal lung tissues, indicating altered expression in cancer.
