| Author: | Lau, Fidelia Sharon |
| Title: | Co-expression analysis reveals ERBB2- and NPM1 associated gene network in relapse HER2-positive breast cancer |
| Advisors: | Yung, Y. M. Benjamin (HTI) Wong, S. C. Cesar (HTI) |
| Degree: | Ph.D. |
| Year: | 2021 |
| Subject: | Breast -- Cancer -- Treatment Breast -- Cancer -- Genetic aspects Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | xxiii, 179 pages : color illustrations |
| Language: | English |
| Abstract: | Background: Breast cancer is the most frequent cancer in women worldwide and is one of the leading causes of cancer-related deaths in both sexes. About 25% of all breast cancer cases are HER2-positive, characterized by high recurrence and mortality rates. In the last twenty years, the development of HER2-targeted therapy has significantly improved patient survival and drastically transformed the course of breast cancer treatment. While most patients are therapy-responsive, some are not, and a subset of those who initially responded experience tumor relapse. This means that there is heterogeneity in treatment response. Co-expression analysis has recently attracted increasing attention in the study of various diseases, particularly in cancer. Since functionally related genes or genes belonging to the same biological pathway typically share similar expression profiles, we are interested in exploring genome-wide co-expression patterns unique to non-relapse and relapse patients. Comparison of their gene co-expression profiles may reveal distinctive properties and mechanisms pertaining to their state and improve our understanding of relapse biology in HER2-positive breast cancer. Nucleophosmin 1 (NPM1) is an important multifunctional nuclear protein and a key player in several malignancies. However, its contribution to breast cancer is not fully understood. Using whole-genome expression data, we will study ERBB2- and NPM1-specific co-expression profiles. We will also be examining the roles of hub genes, transcription factors, and microRNAs in disease relapse. Altogether, we will look at non-coding and coding co-expression patterns and the importance of ERBB2 and NPM1 in non-relapse and relapse HER2-positive breast cancer patients. Results and conclusion: Using our group's structural co-expression analysis approach, we identified genes that are strongly co-expressed with ERBB2 and NPM1 unique to each state. Functional enrichment shows that there is a strong association of ERBB2 with immune-related genes involved in lymphocyte activation and proliferation, and cell cycle pathways in non-relapse patients. Analyses of hub genes, transcription factors, microRNAs, and NPM1-coexpression profiles also reveal strong associations with genes belonging to these biological processes. Interestingly, some of these genes are strongly associated with ERBB2 in non-relapse patients and only become strongly associated with NPM1 in relapse patients. This finding discloses a potential cooperative role of ERBB2 and NPM1 that has never been reported before in governing the biological mechanisms in HER2-positive tumor relapse. |
| Rights: | All rights reserved |
| Access: | open access |
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