Zollo, Immacolata (2023) The role of biomarkers in endometrial cancer: first steps towards large-scale screening and personalized therapy. [Tesi di dottorato]

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Abstract

Endometrial cancer (EC) is the 6th most common cancer in women worldwide with an increasing mortality rate. Currently, the diagnosis of this cancer is based on invasive and painful methods which are performed in presence of symptoms. If on the one hand the symptoms may indicate a more advanced stage of the tumor, on the other they may be linked to non-malignant pathological conditions. This particularly highlights the need for serum biomarkers that can both help the early detection of EC and avoid women without cancer to undergo an invasive test. Many studies have shown significantly different levels of biomolecules between EC patients and healthy controls. However, the detection of these putative biomarkers is always based on traditional methods, like ELISA assays, that are not suitable for a point-of-care (POC) application. An alternative detection method is represented by optical biosensors exploiting the phenomenon of Metal Enhanced Fluorescence (MEF). Biosensors are easy-to-use and cost-effective devices that allow multiplex real-time measurements of very low levels of biomarkers. They can be functionalized with antibodies or complementary nucleic acid probes depending on the target to be detected. The interaction between biomarkers and biorecognition molecules is converted into a quantifiable signal which is enhanced with the use of plasmonic nanostructured surface. In the present study, optical biosensors have been developed and functionalized through Photochemical Immobilization Technique to detect serum diagnostic biomarkers of EC. The preliminary data obtained show the great potential of these devices in the use of a first level screening to distinguish a biological condition from a pathological one. Furthermore, fast-response analysis and multiplex measurements capability make optical biosensors powerful tools that would be well suited for large-scale screening. Besides the role in the diagnosis, tumor markers can be used in the prognostic assessment and in the choice of therapeutic treatment when their levels affect the sensitivity to specific drugs. In light of this, we additionally investigated the biological function of CIP2A, a protein found over-expressed in a variety of cancers, including EC, to assess its possible role as prognostic and therapeutic biomarker. We found that in leukemic cell models the down-regulation of CIP2A increases cell sensitivity to proteasome inhibitor Carfilzomib and affects cell proliferation. Although the effects we observed need to be confirmed in an endometrial cell model, these results suggest that CIP2A might be a promising target for cancer therapy.

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