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        <datestamp>2026-10-01T16:50:53Z</datestamp>
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          <dc:title>Investigating the clinical and molecular significance of &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; in breast cancer</dc:title>
          <dc:creator>Alexa Little (24166974)</dc:creator>
          <dc:subject>PUREID: 473913692</dc:subject>
          <dc:subject>Breast cancer</dc:subject>
          <dc:subject>microbiome</dc:subject>
          <dc:subject>Fusobacterium nucleatum</dc:subject>
          <dc:description>Breast cancer was the most commonly diagnosed cancer worldwide in 2020 (1). Greater understanding of the factors which promote tumour progression and metastatic development is required to improve mortality from this disease. In recent years, a distinct microbiome has been detected in the breast (2). The oral anaerobic bacterium, &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; is enriched in breast tumour tissue compared to matched healthy tissue and is associated with mammary tumour growth and metastatic progression in mouse models (2, 3). Additionally, in colorectal and oral cancers, &lt;i&gt;F. nucleatum&lt;/i&gt; is shown to modulate metastasis, immune escape and inflammation within the tumour microenvironment (4, 5). This thesis aimed to investigate the clinical and molecular implications of &lt;i&gt;F. nucleatum&lt;/i&gt; on the tumour microenvironment and progression of breast cancer.&lt;br&gt;&lt;br&gt;Here, the prevalence, location, and clinicopathological characteristics of &lt;i&gt;F. nucleatum&lt;/i&gt; was investigated using an RNA in situ hybridisation technology (RNA-scope®) and using RNA-sequencing data in 3 different breast cancer cohorts, confirming the presence of the bacterium within the tumour tissue. &lt;i&gt;F. nucleatum&lt;/i&gt; presence within the breast cancer cohorts was correlated with clinicopathological features, identifying a significant association between&lt;i&gt; F. nucleatum&lt;/i&gt; and higher grade tumours. Gene expression data from these breast cancer cohorts confirmed a novel immunomodulatory role of &lt;i&gt;F. nucleatum&lt;/i&gt; within the breast tumour microenvironment. Meanwhile, in vitro co-culture assays demonstrated, for the first time in breast cancer cells, the ability of &lt;i&gt;F. nucleatum&lt;/i&gt; to invade, stimulate inflammatory signalling and promote migration.&lt;br&gt;&lt;br&gt;This research highlights the importance of host-microbial interactions in the context of cancer progression by investigating the relationship between &lt;i&gt;F. nucleatum&lt;/i&gt; and breast cancer. Currently, the mechanisms as to how &lt;i&gt;F. nucleatum&lt;/i&gt; contributes to breast cancer progression and metastatic development are poorly understood. The results of this project evidence a potential role of &lt;i&gt;F. nucleatum&lt;/i&gt; in the promotion of an inflammatory tumour microenvironment and in the progression of breast cancer. By better understanding the consequences of the intra-tumoral presence of this bacteria, it will provide valuable insights into the role of the microbiome in breast cancer progression. This could be harnessed to develop novel biomarkers to predict outcome and/or modulated to enhance treatment efficacy and patient outcome. &lt;br&gt;&lt;br&gt;&lt;i&gt;Thesis embargoed until 31st July 2028&lt;/i&gt;.&lt;br&gt;&lt;br&gt;&lt;br&gt;</dc:description>
          <dc:date>2026-10-01T16:50:53Z</dc:date>
          <dc:type>Text</dc:type>
          <dc:type>Thesis</dc:type>
          <dc:identifier>10.17034/32635200.v1</dc:identifier>
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          <dc:rights>All Rights Reserved</dc:rights>
          <dc:rights>Open Access after 2028-07-31</dc:rights>
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