Evaluation of OTX1 as a potential biomarker of bladder cancer

Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide. With no suitable and validated biomarkers of diagnosis and prognosis, patients are plagued with a high risk of recurrence and progression resulting in significantly increased rate of morbidity and mortality. OTX1 has be...

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Bibliographic Details
Main Author: Baharudin, Aminuddin
Format: Thesis
Language:English
Published: 2018
Subjects:
Online Access:http://psasir.upm.edu.my/id/eprint/84210/1/FPSK%20%28m%29%202019%2032%20UPM%20ir.pdf
http://psasir.upm.edu.my/id/eprint/84210/
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Summary:Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide. With no suitable and validated biomarkers of diagnosis and prognosis, patients are plagued with a high risk of recurrence and progression resulting in significantly increased rate of morbidity and mortality. OTX1 has been implicated as a potential oncogene in several cancers but how OTX1 actually contributes to bladder cancer formation is still poorly understood. Hence, I aimed to evaluate OTX1 as a potential biomarker for bladder cancer in this study. To achieve that, I studied the mRNA expression of OTX1 across a series of bladder cancer cell lines via RT-qPCR and conducted OTX1 siRNA knockdown to reduce the expression of OTX1 in vitro. To observe the effects of knockdown on the migratory rate of cells, migration assay was conducted. The mRNA expression in cancer stem cells in vitro and protein expression of OTX1 in bladder cancer tissues was also investigated via RT-qPCR and IHC respectively. In addition, I attempted to discover the potential of OTX1 as a biomarker of response to predict Newcastle Disease Virusmediated oncolysis by correlating the expression of OTX1 with IC50 values of cell lines infected with NDV. I found that OTX1 was expressed in most bladder cancer cell lines. No significant difference in migratory rate was seen when OTX1 was knockdown in HTB-4. Intriguingly, OTX1 was significantly overexpressed in spheroid cultures compared to monolayer cultures. Using Spearman correlation, I found significant correlation between the protein expression of OTX1 with grade 2 and 3 bladder tumours and using Pearson correlation, weak correlation was found between the fold changes of OTX1 with the IC50 values across similar bladder cancer cell lines. Continuing to expand the findings from this study may lead to a deeper and clearer understanding of the potential role of OTX1 as a biomarker for bladder cancer management.