Accelerated carcinogenesis of colorectal cancer

Lam, XiuQian (2021) Accelerated carcinogenesis of colorectal cancer. MRes thesis, University of Nottingham.

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Abstract

Background: Colorectal cancer (CRC) is a heterogeneous disease with genetic and biochemical dysregulation background. The dysregulation happens in a few important signalling pathways, including Ras signalling, p53 signalling and Wnt/β-catenin signalling. This will lead to the malignant transformation of a normal cell to a cancer cell. Cancer cells are mainly caused by the alterations of multiple tumour suppressor genes and oncogenes. Research analysis was conducted to identify a better survival rate and prognosis outcome on colorectal tumours, especially in this study where the expression of tumour protein 53 (TP53) and B-cell lymphoma 2 (Bcl-2) biomarkers via immunohistochemical staining were targeted.

Methods: Tissue microarray and manual histopathological scoring were conducted in this study, with a cohort of 1000 cases. Statistical results were also reported to enable analysis of the estimated H-score. Quartiles were used to determine the cut-off points of the H-score. TP53 and Bcl-2 staining were only defined when the core staining is more than 15% of tumour cells. TP53 expression, Bcl-2 expression and the proportion of tumour epithelium to stroma in colorectal carcinoma were studied in a series of 880 patients (382 females; 498 males). Its relation to multiple clinicopathological variables and survival probability were also assessed. The involvement of TP53 and Bcl-2 mutations in the pathogenesis of colorectal cancer and their prognostic impact were highlighted. Correlations on tumour-stroma ratio (TSR) and the survival probability can also be determined by statistical test (p-value), with p-value < 0.05 showed their significance. Immunohistochemistry was used to assess the number of peritumoural lymphocytes for an objective manner, according to standardized histopathology.

Results: High TP53 and low Bcl-2 expression were identified as good prognostic factors, providing a favourable outcome, with p-value < 0.05. The median score for TP53 was 30, with 436 (49.55%) of tumours showed high expression. Whilst there were 498 (56.59%) tumours that had low expression of Bcl-2, with a median score of 10. By comparing tumour and normal CRC samples, TP53 was highly expressed in tumour-derived CRC samples. Whereas Bcl-2 was observed with similar expression to normal samples, predominantly because it has a lower expression within tumour cells. Low tumour-stroma ratio (TSR) was detected with lower survival probability on TP53 biomarker for the identification of CRC patients, providing with a favourable outcome. Several reliable methods were given to have a better prognostic impact and treatments on CRC.

Conclusion: Treatment of cancer is directly based on their stage. To provide a proper cancer treatment for the matching patient at the right time, this study is crucial to give a beneficial outcome on CRC cells and a chance of treatment success.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Ilyas, Mohammad
Keywords: Colorectal cancer; Tumour protein 53; B-cell lymphoma 2; Biomarkers
Subjects: W Medicine and related subjects (NLM Classification) > WI Digestive system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 65081
Depositing User: LAM, XIU
Date Deposited: 04 Aug 2021 04:41
Last Modified: 04 Aug 2021 04:41
URI: http://eprints.nottingham.ac.uk/id/eprint/65081

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