Loading...
Changes in selective biomarkers after transurethral resection of the bladder tumour (TURBT), and their association with Non-muscle invasive bladder cancer (NMIBC) recurrence and progression
Ella-Twongiis, Peter
Ella-Twongiis, Peter
Advisors
Editors
Other Contributors
Affiliation
EPub Date
Publication Date
2019-10-01
Submitted Date
Collections
Files
Loading...
Thesis
Adobe PDF, 18.12 MB
Other Titles
Abstract
Introduction
Bladder Cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases
annually. It affects more men than women (ratio 3:1). Major risk factors include tobacco,
chemical carcinogens, schistosomiasis infection and age. About 75-85% of BC are non-muscle
invasive (NMIBC), which is associated with high recurrence and progression rates (50-60%
within 7-10 years). Currently, diagnosis, treatment and management of BC is via clinical
procedures such as transurethral resection of the bladder tumour (TURBT) and endoscopy.
Concerning laboratory investigations, there are no routine biomarkers currently available for
identifying BC patients at increased risk of developing recurrence and progression. By
monitoring changes in selective biomarkers post-TURBT, any sustained changes may be a
predictor of cancer recurrence or progression. The main-focus of this research study was to
evaluate changes in selective novel biomarkers and their association with recurrence and
progression in BC.
Materials & Methods
In this research, 40 patients (n=40) scheduled for TURBT at the Wrexham Maelor Hospital, North
Wales were recruited after written informed consent. Ethical approval for the project was granted
via IRAS (REC4: 14/WA/0033). Venous blood samples were taken at baseline (pre-operative) and
following TURBT surgery at 1, 3 and 6 months post-operatively. Bladder tumour samples were
also taken during TURBT according to standard procedure.
Selective biomarkers to assess inflammation, angiogenesis and tumour growth, were measured
using commercially available ELISA and BioPlex multiplex assay kits. Tissue immunoreactivity
of novel biomarkers were also assessed in BC tissues using immunohistochemistry, with clinical
outcome measures being recorded for all patients.
Results
Significant increases in serum Cluster of differentiation 31 (CD31) (p=0.003) and Stem Cell
Factor (SCF) (p=0.032) concentration, as well as trends of increasing concentration of serum
basic Fibroblast Growth Factor (bFGF) (p=0.14), Vascular Endothelial Growth Factor
Receptor-1 and 2 (VEGFR-1) (p=0.15), VEGFR-2 (p=0.15) and Follistatin (p=0.40) were
observed in BC patients up to 6 months post-operative.
There were also significant decreases in serum Macrophage Inflammatory Protein -2 (MIP-2)
(p=0.001), Platelet Derived Growth Factor (PDGF) (p=0.012), Matrix Metalloproteinase-9
(MMP-9) (p=0.002) and Vascular Endothelial Growth Factor C (VEGF-C) (p=0.04) serum
concentration. Trends of decreasing concentration in MMP-2 (p=0.79), MMP-3 (p=0.15),
interleukin-6 (IL-6) (p=0.26), interleukin-8 (IL-8) (p=0.15) and tumour necrosis factor-α (TNF-α)
(p=0.69) were observed in BC patients up to 6 months post-operative.
There was significant immunoreactivity of CD31 (p< 0.001), CD34 (p< 0.001), Human
epidermal growth factor receptor-2 (HER-2) (p=0.032), S100P (p< 0.001), Cyclooxygenase-2
(COX-2) (p< 0.001), VEGFR-3 (p< 0.001), SOX-2 (p< 0.001) and thrombomodulin (p=0.010)
in bladder tumours. Although recurrence was significantly associated with cancer grade, there
was no association with antibody immunoreactivity.
Conclusion
Findings from the present study may indicate an alternative approach in the monitoring and
management of patients with BC. It is proposed that by allowing urological surgeons access to
laboratory markers such as MIP-2, MMP-9, PDGF, SCF, HER-2, Thrombomodulin and CD31
(biomarker profile), potentially, in the future, these biomarkers may be used in addition to, or
in combination with, currently used scoring systems to predict cancer recurrence and
progression. However, verification and validation of these biomarkers are needed using larger
cohorts.
Citation
Ella-Twongiis, P. (2019). Changes in selective biomarkers after transurethral resection of the bladder tumour (TURBT), and their association with Non-muscle invasive bladder cancer (NMIBC) recurrence and progression (Doctoral dissertation). University of Chester, UK.
Publisher
University of Chester
Journal
Research Unit
DOI
PubMed ID
PubMed Central ID
Type
Thesis or dissertation
Language
en