Glycomics of different cell types in ascites of ovarian cancer patients

<p dir="ltr">High grade serous ovarian cancer (HGSOC) has the highest mortality rate of the gynaecological cancers. Improving patient prognosis hinges on tracking the effectiveness of a treatment course and accurately diagnosing the organ of origin. Current blood biomarkers are unreliable for this purpose, and ascites fluid, a hallmark of late-stage HGSOC removed during treatment presents a potentially unique source of new biomarkers, particularly of treatment response. This thesis assessed <i>N</i>- and <i>O</i>glycosylation differences between total ascites cells and three distinct cell sub-populations isolated according to marker status: cancer (CD45-/EpCAM+), immune (CD45+) and marker-negative (CD45- /EpCAM-) cells to determine baseline glycosylation before treatment. Using samples from nine individuals and liquid chromatography mass spectrometry glycomics, expression of isomeric differences in the <i>N</i>- and <i>O-</i>glycan signatures between ascites cell populations was observed. Cancer cells of a tubal origin clustered together with cells of an ovarian origin by Principal Component Analysis, contrasting with immune cells which clustered separately depending on cancer origin. This implies a shared cancer pathology but different immunological responses, thus differentiating HGSOCs of ovarian or tubal origin. The differences in glycomes, lay groundwork for tracking glycomic signature changes in sorted ascites cells over a treatment course as well as the clinical diagnosis of organ of origin.</p>