Abstract
Glutathione-S-transferases (GST) enzymes detoxify xenobiotics and are implicated in response to anticancer therapy. This study evaluated the association of GST theta 1 (GSTT1), GSTT2, and GSTT2B with Mycobacterium bovis Bacillus Calmette–Guérin (BCG) response in non-muscle-invasive bladder cancer treatment. In vitro assessments of GSTT2 knockout (KO) effects were performed using cell lines and dendritic cells (DCs) from GSTT2KO mice. Deletion of GSTT2B, GSTT1, and single-nucleotide polymorphisms in the promoter region of GSTT2 was analysed in patients (n = 205) and healthy controls (n = 150). Silencing GSTT2 expression in MGH cells (GSTT2BFL/FL) resulted in increased BCG survival (p < 0.05) and decreased cellular reactive oxygen species. In our population, there are 24.2% with GSTT2BDel/Del and 24.5% with GSTT2BFL/FL. With ≤ 8 instillations of BCG therapy (n = 51), 12.5% of GSTT2BDel/Del and 53.8% of GSTT2BFL/FL patients had a recurrence (p = 0.041). With ≥9 instillations (n = 153), the disease recurred in 45.5% of GSTT2BDel/Del and 50% of GSTT2BFL/FL. GSTT2FL/FL patients had an increased likelihood of recurrence post-BCG therapy (HR 5.5 [1.87–16.69] p < 0.002). DCs from GSTT2KO mice produced three-fold more IL6 than wild-type DCs, indicating a robust inflammatory response. To summarise, GSTT2BDel/Del patients respond better to less BCG therapy and could be candidates for a reduced surveillance regimen.
Share and Cite
MDPI and ACS Style
Rahmat, J.N.; Tham, S.M.; Ong, T.L.; Lim, Y.K.; Patwardhan, M.V.; Nee Mani, L.R.; Kamaraj, R.; Chan, Y.H.; Chong, T.W.; Chiong, E.;
et al. Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette–Guérin Immunotherapy in Bladder Cancer Patients. Int. J. Mol. Sci. 2024, 25, 8947.
https://doi.org/10.3390/ijms25168947
AMA Style
Rahmat JN, Tham SM, Ong TL, Lim YK, Patwardhan MV, Nee Mani LR, Kamaraj R, Chan YH, Chong TW, Chiong E,
et al. Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette–Guérin Immunotherapy in Bladder Cancer Patients. International Journal of Molecular Sciences. 2024; 25(16):8947.
https://doi.org/10.3390/ijms25168947
Chicago/Turabian Style
Rahmat, Juwita N., Sin Mun Tham, Ting Li Ong, Yew Koon Lim, Mugdha Vijay Patwardhan, Lata Raman Nee Mani, Revathi Kamaraj, Yiong Huak Chan, Tsung Wen Chong, Edmund Chiong,
and et al. 2024. "Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette–Guérin Immunotherapy in Bladder Cancer Patients" International Journal of Molecular Sciences 25, no. 16: 8947.
https://doi.org/10.3390/ijms25168947
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details
here.
Article Metrics
Article Access Statistics
For more information on the journal statistics, click
here.
Multiple requests from the same IP address are counted as one view.
, 