Glycoproteomic characterization of Lipoprotein (a) as a novel biomarker for early detection of ovarian cancer
Description: There has been tremendous progress in recent years in decreasing cancer mortality rates and increasing cancer survivorship. There are, however, still diseases where early detection and thus prognosis remains poor. In epithelial ovarian cancer (OC) the 5-year survival rate is still poor, mainly because most patients (70%) are diagnosed in advanced International Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease, when the tumor has spread within the abdomen and beyond. No screening method has been found so far and the established methods like tumor marker CA 125 and transvaginal ultrasound, combined in various ways and algorithms have not shown any effect on outcome of the affected patients (1, 2). Focus of the research in this field should be therefore primarily the identification of different early detection methods to identify the disease as an even earlier stage where treatment can be curative.The objective of this study is (A) to explore a novel method for screening and diagnosis of OC based on the glycoconjugate characterization of the biomarker Lipoprotein (a) [(Lp(a)], that has been indicated to exhibit an OC specific form of glycosylation in the serum of OC patients, and (B) to perform a pilot study on a cohort of early ovarian cancer patients from Basel.Protein glycosylation is involved in various cellular processes and altered cellular glycosylation is well understood to be intrinsically involved in tumor development and metastasis (3-5). Hence, protein-specific glycosylation features that are associated with the pathogenesis of a tumor are highly promising to deliver novel early stage tumor biomarkers (6-8).Indeed, the detection and measurement of specific glyco-forms of a certain protein or lipid could contribute to the early recognition of cancer or for diagnosis at a pre-cancerous stage (9). Nevertheless, to date it has remained unclear which proteins or glycolipids are in fact carrying these specific sugar modifications in the serum of OC patients.Preliminary data indicate that the occurrence of specific fucose-containing signals detected by MR spectroscopy are correlated with moderate to poorly differentiated malignancy and have been detected in the Lp(a) fraction only in the serum of cancer patients. Therefore, we aim to apply the latest glycomic/glycoproteomic techniques to sequence the Lp(a) associated glycans from OC cancer patient sera and healthy controls. Subsequently, we intend to identify Lp(a) specific glycosylation features representative for early OC, having at our disposal matched blood and tumor samples of 100 Australian OC patients (testing cohort) and a cohort of 50 newly diagnosed early stage (FIGO I/II) epithelial ovarian cancers for the pilot study.Applying newly developed high-throughput glycomic platform technologies, together with the analysis of large cohorts of patient samples, we will be able to establish novel assays for Fucose-carrying Lp(a) as a biomarker for early-stage OC. This might develop into a more sensitive biomarker, which can identify this disease at a preclinical stage and thus make an impact on the outcome of our patients.
Amount: CHF 153,800
Funding type: fellowship
Funder scheme: Postdoc.Mobility
Start date: 2023-07-01
End date: 2025-06-30
Investigator: Tozzi, Alessandra
Institution: Institution abroad - Australia
Subfield: Cancer Research
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 210932
OpenAlex ID: G3094839857