Citation
Baharudin, Aminuddin
(2018)
Evaluation of OTX1 as a potential biomarker of bladder cancer.
Masters thesis, Universiti Putra Malaysia.
Abstract
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.
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