| Author: | Tse, Yin Suen |
| Title: | Investigation of hypoxia-induced novel alternative proteins in Hepatocellular Carcinoma with a multi-omics approach |
| Advisors: | Zhao, Qian (ABCT) |
| Degree: | M.Phil. |
| Year: | 2024 |
| Subject: | Liver -- Cancer -- Treatment Proteomics Anoxemia Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | 94 pages : color illustrations, map |
| Language: | English |
| Abstract: | Hepatocellular carcinoma (HCC) represents the predominant form of primary liver cancer, accounting for the majority of cancer-related deaths worldwide. Conventional treatments are only effective for patients with early-stage disease. The propensity for late-stage diagnosis, coupled with the restricted spectrum of available treatment interventions, significantly contributes to the high mortality rates associated with HCC. It has recently been recognised that alternative proteins (AltProts), which originate from non-coding regions, represent a promising new avenue for therapeutic intervention. Despite their crucial role in cancer progression, the identification of AltProts remains challenging. Hypoxia, defined as a condition characterized by low oxygen levels, is a common feature of HCC and contributes to its progression. There has been a paucity of empirical research conducted to delineate the existence and function of AltProts under hypoxic conditions. In order to address these research interests, two objectives were focused in this study: (i) to optimise the workflow of the discovery of novel AltProts; (ii) to elucidate the functional significance of these AltProts under hypoxic conditions in HCC. A multi-omics approach was employed by combining transcriptomics data to build an in-house database for mass spectrometry-based proteomics analysis. A set of hypoxia-induced AltProts were successfully identified, revealing a distinct expression pattern under hypoxic conditions. One AltProt of particular interest, designated Hpx1, demonstrated upregulation under hypoxic conditions and was implicated in several critical cellular processes. The amino acid sequence of Hpx1 exhibited a high degree of conservation. Analysis of multiple public HCC clinical datasets revealed that Hpx1 expression was elevated in tumor tissues relative to normal hepatic samples. Functional assays conducted in vitro under hypoxic conditions indicated that Hpx1 promoted cell proliferation and migration, thereby suggesting a contributory role in the tumorigenic process of HCC. In summary, this study provides novel insights into the role of hypoxia-induced AltProts in HCC and highlights their potential as therapeutic targets. The multi-omics approach presented herein represents a robust and innovative approach for the identification and characterization of novel AltProts in cancer biology, stimulating the development of innovative therapeutic strategies. |
| Rights: | All rights reserved |
| Access: | open access |
Copyright Undertaking
As a bona fide Library user, I declare that:
- I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
- I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
- I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.
By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.
Please use this identifier to cite or link to this item:
https://theses.lib.polyu.edu.hk/handle/200/13532