Abstract
BackgroundThe aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients.MethodsExpression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity.ResultsT-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2–T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p < 0.0001) is significantly higher than in invasive bladder tumors and in patients with high-grade bladder carcinoma, respectively. In addition, heavy smokers, whose tumors express low levels of GATA-3 and Bcl-6, are poor responders to BCG (p = 0.01 and p = 0.03). Finally, better patient survival correlated with GATA-3 (p = 0.04) and Bcl-6 (p = 0.04) but not T-bet expression.ConclusionsOur results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.
Highlights
The aim of this study was to investigate the clinical significance of three immune cell-related transcrip‐ tion factors, T-box master transcription factor regulator (T-bet), trans-acting T cellspecific transcription factor 3 (GATA-3) and B-cell lymphoma 6 transcription factor (Bcl-6) in bladder cancer in Tunisian patients
T‐bet expression in bladder tumor Expression of the Th1 transcription factor T-bet in bladder carcinoma was determined by real-time PCR as a function of the tumor node metastasis (TNM) histological stage of the disease
We were unable to associate the expression of GATA-3 to T helper2 (Th2) or another type of cell, it remains possible that this transcription factor serves as a good prognosis biomarker in bladder cancer, since its expression is associated with patient survival
Summary
The aim of this study was to investigate the clinical significance of three immune cell-related transcrip‐ tion factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. Bahria‐Sediki et al J Transl Med (2016) 14:144 attested that the master regulator of Treg differentiation Foxp-3 is expressed This creates an immunosuppressive microenvironment leading to tumor progression [8]. The Th2 response, evidenced inter alia by the expression of GATA-3, was associated with tumor immune evasion in a mouse study [10], but was not associated with a clinical outcome in human studies [11, 12] or in patient’s prognosis [13]. Where the Tfh presence is significant, it has been associated with a better patient cancer outcome (breast cancer) [17], whereas a decreased proportion of Tfh was associated with increased hepatocellular carcinoma disease progression [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
