Investigating PCSK9 expression using oropharyngeal tissue samples

  • Research type

    Research Study

  • Full title

    Investigating PCSK9 protein expression in normal oropharyngeal mucosa and oropharyngeal squamous cell carcinoma.

  • IRAS ID

    305077

  • Contact name

    Mark Gormley

  • Contact email

    mark.gormley@nhs.net

  • Sponsor organisation

    University of Bristol

  • Duration of Study in the UK

    1 years, 0 months, 1 days

  • Research summary

    Research Summary
    Background

    Taking cholesterol-lowering drugs such as PCSK9 inhibitors, may alter the risk of getting certain cancers, but the evidence surrounding head and neck cancer is inconclusive. In addition, the mechanisms by which the PCSK9 gene might play a role in head and neck cancer requires further evaluation.

    Cholesterol-lowering medication use modifies circulating blood factors such as cholesterol, hormones and metabolites which result in the exposure of cells to an environment which may lead to cancer. Recent genetic epidemiology and in vivo studies carried-out by our research group suggest PCSK9 inhibition may increase the risk of head and neck cancer, particularly in the oropharyngeal (throat) subsite.

    As this is a novel finding, we want to first determine PCSK9 is expressed differently in human oropharyngeal cancer tissue compared to normal tonsil tissue.

    Research approach

    To determine if PCSK9 is expressed in vivo within normal oropharyngeal mucosa (tonsil tissue) and if PCSK9 expression is altered in oropharyngeal squamous cell carcinoma (throat cancer) tissue. We will perform immunohistochemistry on human tissue samples that have been removed for diagnostic or treatment purposes.

    Immunohistochemistry involves selectively identifying antigens (proteins the body’s immune system recognises) in cells within tissues, through the binding of antibodies (protective proteins) to them.

    Expected impact

    We aim to investigate if there is a link between PCSK9 protein expression and the development of oropharyngeal (throat) cancer in vivo, which could help inform drug choices or targeted cancer prevention and intervention for these patients.

    Lay summary of study results: It was very difficult to stain for the PCSK9 protein in oropharyngeal tissue, with a high level of background no matter what dilution was used. We were unable to reproduce a reliable result and therefore agreed to discontinue the project.

  • REC name

    London - West London & GTAC Research Ethics Committee

  • REC reference

    22/PR/0087

  • Date of REC Opinion

    11 Feb 2022

  • REC opinion

    Favourable Opinion