Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Faculty of Health and Social Sciences | en_US |
| dc.contributor.advisor | Law, Ka Wai Helen (HTI) | en_US |
| dc.creator | Lau, Matthew Y. H. | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/14198 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | en_US |
| dc.rights | All rights reserved | en_US |
| dc.title | Radiation-induced glycolytic gene expression in colorectal cancer cells | en_US |
| dcterms.abstract | Originating from the colon and/or rectum, CRC is the third most common cause of cancer deaths in Hong Kong in 2022 with thousands of new cases reported annually. Frequently, RT is used as a neo-adjuvant measure before surgery. However, while some patients experience a higher response rate by showing greater tumour size reduction, other patients may not see definitive results, causing a difference in CRC radio-response. Previous work in our team on mouse xenografts have identified several metabolic proteins that are upregulated in irradiated samples exhibiting poor radio-response. Out of the proposed markers, GAPDH, PGK1, PGAM1, ENO1 and PKM1 were found to be directly associated with glycolysis. Following this observation, the current project aimed to understand the significance of glycolytic gene expressions in the radio-response of CRC cell lines. By achieving this, valuable insights and novel foundations will be provided to both carcinogenesis and cancer treatment, especially in the molecular diagnostics and research specialty. | en_US |
| dcterms.abstract | As part of the data mining process, a systematic review was performed according to the PRISMA guidelines, providing an overview of the molecular mechanisms that affect CRC patients' radio-response. Out of 56 reviewed genes, GSEA identifies 24 to be correlated to pathways related to radio-response upon which 15 were found to be associated with the cancer metabolism pathway. In view of this, first the SF2 of mammalian CRC cell lines HCT116, DLD1 and SW480 were determined via clonogenic assay. Based on SF2 values, SW480 is the most radio-sensitive (SF2: 0.33 ± 0.02). HCT116 have the highest viability (SF2: 0.43 ± 0.03) closely followed by DLD1 (SF2: 0.41 ± 0.06). CRC cell lines were then irradiated with 2 Gy and harvested at 1, 4, and 12 hours post-irradiation. RNA was extracted and reverse transcribed into cDNA. SYBR green-based qPCR was performed to obtain gene expression data. In order to validate housekeeping genes stability, GAPDH, β-ACT and IPO8 expressions were analyzed by BestKeeper algorithm. Amongst the three housekeeping genes, β-ACT exhibits the least fluctuations and is therefore the most suitable to be used to normalize relative fold changes of GAPDH, PGK1, PGAM1, ENO1 and PKM1 by the 2⁻(-ΔΔCt) calculation. Results from each cell line were separately compared with its corresponding non-irradiated control to determine changes in expression level at each time point through paired T-test using the PRISM software, with a p-value < 0.05 indicating significant differences. Interestingly, each cell line manifested a unique expression trend which are comparable in both irradiated and non-irradiated groups. Furthermore, PGK1 and ENO1 were found to be significantly lower expressed at specific time points in irradiated DLD1 and SW480. | en_US |
| dcterms.abstract | The work demonstrated in this thesis provides evidence showing how cell lines representing different CRC stages display distinctive radio-response through differential expression of glycolytic genes. By identifying the post-irradiation expression patterns of key glycolytic markers, this research reinforces our understanding of cancer metabolism radio-response and offers potential targets for enhancing CRC radio-sensitivity. Moreover, substantial implications contributing to the development and improvement of personalized therapeutic strategies are presented. | en_US |
| dcterms.extent | xv, 290 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2025 | en_US |
| dcterms.educationalLevel | DHSc | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.accessRights | restricted access | en_US |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 8651.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 4.3 MB | Adobe PDF | View/Open |
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