Learn about the challenges in diagnosing epithelial ovarian cancer (EOC) and the importance of early detection. Discover promising advancements in blood tests for identifying high-risk patients, potentially revolutionizing EOC diagnosis and treatment outcomes.
Epithelial ovarian cancer (EOC) represents the most significant number of deaths from cancers of the female reproductive system.
Although effective treatments are available in the early stages of EOC, timely diagnosis is difficult due to nonspecific presentation and signs. Therefore, there has been great interest in developing systems that can identify patients at high risk of receiving an EOC diagnosis before the disease spreads and progresses.
A new article published in the British Journal of Cancer explores the potential usefulness of glycoproteins as biomarkers of EOC. In the future, these types of models could allow the diagnosis of EOC to be made from a blood test.
Existing diagnostic guidelines:
Currently, a sequence of diagnostic tests is used to stage EOC, including imaging and blood tests for CA-125, an epithelial surface protein released from EOC cells. However, these approaches lack specificity and their sensitivity remains low in early EOCs.
Additionally, about 20% of COEs do not have increased CA-125. In fact, CA-125 levels may increase in other non-cancerous gynecological conditions such as endometriosis and uterine fibroids. Therefore, CA-125 may be a more reliable marker to monitor cancer progression and treat EOC.
Early EOC is often overlooked, and non-cancerous conditions presenting with a pelvic mass are often prioritized for surgery. Ultimately, only about 20% of all pelvic masses are malignant, while up to 33% of early EOCs are more advanced after histological examination.
There is an unmet clinical need for sensitive and specific tests for early detection, staging of ovarian cancer, and evaluation of malignant versus benign pelvic masses.
The current study used a case-control design to analyze serum glycoproteins using mass spectrometry, coupled with artificial intelligence (AI), to identify those that can distinguish EOC from other conditions and differentiate late from early EOC. A classification system using these markers was then constructed and used to explore the underlying mechanisms that could explain these changes.
EOC versus non-cancerous masses:
A total of 27 differential biomarkers were identified, including several associated with ovarian cancer, such as alpha-1-antichymotrypsin, alpha-1-acid glycoprotein 1, and immunoglobulin G (IgG).
Incorporating these glycoproteins into a new classification system for DED showed high accuracy, sensitivity and specificity of more than 85% each, which increased with cancer stage. This model also had a creditable performance when applied to healthy patients, since it presented values similar to those observed with benign tumors.
A prospective study in women with pelvic masses using this model showed similar expression patterns of these biomarkers. In this study, the accuracy, specificity, and sensitivity of the model were reduced to 72%, approximately 50%, and 74%, respectively.
Fucose residues and COE progression:
Fucosylation appears to be increased in the EOC, with tri- and tetraantennary fucosylated N-glycans exhibiting the greatest association with the EOC in a linear manner from early to late stages. As the tumor advanced in stage, there was a progressive shift from non-fucosylated to fucosylated forms of these glycopeptides.
These specific markers could help diagnose late-stage EOC, as a model classifier based on these proteins achieved more than 90% accuracy and 100% sensitivity despite low specificity. With metastatic EOC, fucosylation continued to increase, while the observed differential gene expression suggested highly branched fucosylated N-glycans.
Cytokines and EOC:
Metastatic and late-stage EOC were accompanied by changes in serum cytokines, including interleukin 6 (IL-6), IL-8, IL-10, and monocyte chemoattractant protein 1 (MCP-1).
These biomarkers, which typically originate from the liver and circulating immune cells, have been observed in both late-stage EOC and peripheral tissues of affected individuals. Therefore, common factors triggered by a change in cytokine levels underlie the common glycosylation processes at these sites.
Journal reference:
- Dhar, C., Ramachandran, P., Xu, G., et al. (2024). Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling. British Journal of Cancer. doi:10.1038/s41416-024-02644-4.
- New blood test shows promise in early detection of ovarian cancer : News Medical
