Elucidating the mechanistic role of ovarian cancer biomarkers: Lessons learnt from affinity-proteomics

A salient feature of ovarian carcinoma (OC) is its unique tumor microenvironment (TME) enabling early onset of transcoelomic dissemination via the malignant ascites, with the omentum as a preferred site of tumor metastasis. These traits together with typical late diagnosis and high incidence of chemoresistance render OC the most lethal gynecological malignancy. Deciphering the mechanisms allowing tumor progression and metastasis represents an important aim in OC research. Also, there is a high medical need to identify biomarkers that could serve as diagnostic tools for detection of early and recurrent disease. Due to the easy access, one overarching goal is to define clinically relevant blood biomarkers reflecting the pro-tumorigenic features of the TME. For its part, the ascites better reflects the tumor secretome by holding large amounts of stromal, immune and tumor cells, as well as soluble secreted factors and extracellular vesicles, which justifies a more detailed analysis of the ascites proteome. Despite previous efforts based on mass-spectrometry analyses, biomarkers derived from these studies have so far not been integrated into clinical practice. Novel approaches applying affinity-based proteomics have more recently revolutionized biomarker research by providing systematic high-throughput analysis and highly sensitive detection. In the following, we discuss key findings in OC research applying these approaches to unravel intercellular crosstalk within the TME while identifying novel biomarkers. Understanding the origin, function and clinical impact of putative biomarkers is crucial, not only to depict the intercellular communication in the OC TME, but also to develop targeted therapies and improved diagnostic tools.