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Upregulation of Cytotoxic T-Lymphocyte-Associated Protein 4 and Forkhead Box P3 Transcripts in Peripheral Blood of
Ali Ariafar1, Mojtaba Habibagahi2, Mansooreh Jaberipour3
1Department of Urology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Background:
Regulatory T cells (Tregs) play a key role in the progression of tumors. These cells express forkhead box P3 (FOXP3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which are the potential targets for cancer immunotherapy. The present study aimed to evaluate FOXP3 and CTLA4 transcripts in patients with bladder cancer (BC) compared with healthy individuals.
Methods:
Transcripts of CTLA4 and FOXP3 genes in the peripheral blood mononuclear cells (PBMCs) of 50 patients with histologically confirmed BC and 50 healthy individuals were assessed at the Institute for Cancer Research, Shiraz University of Medical Sciences (Shiraz, Iran) during 2014-2016. RNA was extracted from PBMCs, then cDNA was synthesized and subjected to quantitative real-time PCR (qRT-PCR) using appropriate primers. Statistical analysis was performed using SPSS software (version 21.0).
Results:
Significantly higher amounts of CTLA4 and FOXP3 gene transcripts were found in the peripheral blood of BC patients compared with healthy individuals. The expression of both genes was significantly higher in patients with non-invasive and grade I/II BC. The median of CTLA4 and FOXP3 transcript expressions was 3.74 and 5.39, respectively, in non-invasive BC patients, which was significant compared with the control group (P=0.0016 and P=0.009, respectively). The median of target gene mRNA expression in grade I/II BC patients was 2.9 for CTLA4 and 6.61 for FOXP3, which was significant compared with the controls (P=0.013 and P=0.0037, respectively).
Conclusion:
This study highlights the functional activity of Tregs in early stages of bladder cancer and showed the importance of CTLA4 and FOXP3, when it comes to screening BC.
Insights
Regulatory T cells (Tregs) are crucial in bladder cancer progression. This study found higher FOXP3 and CTLA4 gene expression in bladder cancer patients, indicating their potential role in early cancer detection.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Regulatory T cells (Tregs) influence tumor progression.
- FOXP3 and CTLA4 are key markers of Tregs and potential immunotherapy targets.
- Bladder cancer (BC) is a significant health concern.
Purpose of the Study:
- To evaluate FOXP3 and CTLA4 gene transcript levels in bladder cancer patients.
- To compare these transcript levels with those in healthy individuals.
- To assess the potential of FOXP3 and CTLA4 as biomarkers for bladder cancer screening.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) was used to measure gene transcripts.
- Peripheral blood mononuclear cells (PBMCs) were collected from 50 BC patients and 50 healthy controls.
- Statistical analysis was performed to compare gene expression levels.
Main Results:
- Significantly elevated FOXP3 and CTLA4 transcripts were observed in BC patients compared to controls.
- Higher expression of both genes was noted in patients with non-invasive and low-grade (I/II) bladder cancer.
- Specific median transcript levels for FOXP3 and CTLA4 were reported for non-invasive and grade I/II BC groups, showing statistical significance.
Conclusions:
- The study underscores the functional role of Tregs in early-stage bladder cancer.
- FOXP3 and CTLA4 expression levels are important indicators for bladder cancer screening.
- These findings suggest potential utility of Tregs markers in BC diagnostics.
