Accelerated carcinogenesis of colorectal cancer
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 transformatio...
| Main Author: | |
|---|---|
| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2021
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/65081/ |
| _version_ | 1848800183407607808 |
|---|---|
| author | Lam, XiuQian |
| author_facet | Lam, XiuQian |
| author_sort | Lam, XiuQian |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:47:30Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-65081 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:47:30Z |
| publishDate | 2021 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-650812025-02-28T15:11:48Z https://eprints.nottingham.ac.uk/65081/ Accelerated carcinogenesis of colorectal cancer Lam, XiuQian 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. 2021-08-04 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/65081/1/CRC%20Thesis%20Submission%20%28XiuQian%20Lam%29.pdf Lam, XiuQian (2021) Accelerated carcinogenesis of colorectal cancer. MRes thesis, University of Nottingham. Colorectal cancer; Tumour protein 53; B-cell lymphoma 2; Biomarkers |
| spellingShingle | Colorectal cancer; Tumour protein 53; B-cell lymphoma 2; Biomarkers Lam, XiuQian Accelerated carcinogenesis of colorectal cancer |
| title | Accelerated carcinogenesis of colorectal cancer |
| title_full | Accelerated carcinogenesis of colorectal cancer |
| title_fullStr | Accelerated carcinogenesis of colorectal cancer |
| title_full_unstemmed | Accelerated carcinogenesis of colorectal cancer |
| title_short | Accelerated carcinogenesis of colorectal cancer |
| title_sort | accelerated carcinogenesis of colorectal cancer |
| topic | Colorectal cancer; Tumour protein 53; B-cell lymphoma 2; Biomarkers |
| url | https://eprints.nottingham.ac.uk/65081/ |