The Key To Increasing Ovarian Cancer Survival Rates: Protein Biomarkers

Ovarian cancer (OC) is the 5th leading cause of cancer-related deaths in women. Despite being less common, OC is three times as deadly, due to late diagnoses. These late diagnoses lead to a survival rate less than 30%. Women with OC, before the diagnosis, reported vague abdominal symptoms (VAS), which consists of abdominal and pelvic pain. This pain is very broad and is common in many other conditions, leading to less effective diagnoses.

The lack of effective diagnostic methods proves deadly. Fast growing early-stage OC tumors doubles every 4 months, while late-stage tumors double every 2.5 months. Therefore, finding effective diagnostic methods are crucial (survival rates may jump to 90%).

Methods

Giles and Culp-Hill et al. found a new approach to detecting OC: lipid biomarkers. Previous research on this topic proved that identifying gangliosides could help identify OC tumors. Gangliosides are complex molecules that play roles in cell signaling, cell-to-cell recognition, and immune responses. Gangliosides (in OC, especially GD2 and GD3) are highly expressed on tumor cells and very rarely found in healthy cells. Therefore, they can act as specific biomarkers for detecting cancer.

However, for this research paper, researchers delved into lipidomics, the process of using techniques to identify and characterize all lipids present in a cell, tissue, or organism. Ever since abnormal lipid metabolism was found to be a sign of cancer, lipidomics has become much more relevant.

To do this, researchers analyzed samples to look for changes in the ganglioside profile (a list of different types in the sample) and found that differences between those with OC and those without were subtle. With this information, researchers came to the conclusion that using lipid biomarkers would unearth bigger differences.

Results

The focus was set on early stage OC samples, as lipidomic profiles shift as the disease progresses. Data showed that Lipids 1262 and 455 were significantly altered between the test groups and this pattern was seen with other lipids as well. It was also found that though the individual lipid species between early OC and late-stage OC were different, the specific lipid types were central to the key differences. Therefore, shifts from early-stage to late-stage OC is clear.

Figure 1. OC vs. Controls

The figure above visually shows the difference in lipid species present in those with and without OC. In graph A, it is shown that those with OC have more Cer and DG in their bloodstream, among other obvious differences. These differences are also clearly represented in graph C. In graphs B and D, the finding that the types of lipids in those with OC is different can be supported. Though the cohorts shared some lipid species, there were obvious differences as well.

Discussion

This novel research demonstrates that testing for OC in. symptomatic individuals leads to early detection rates compared to the costly-screening techniques currently available. There is evidence that quick diagnoses are surprisingly important. For instance, a "fast-track pathway" led to early-stage diagnoses in a quarter of the most serious OCs. Most importantly, a majority of those diagnosed in the early-stage saw positive surgical outcomes. This effectively highlights the importance of an early diagnosis.

However, because the test is in its early stages, it has its limitations as well. A CA125 blood test (the lipid blood test) can produce results based on body conditions. In those with endometriosis, fibroids, liver disease, and currently in their menstruation cycle, CA125 is higher. Furthermore, it cannot distinguish between malignant (a tumor that has spread from its original place) and benign tumors.

Even with these limitations, the test is reliable and can detect lipid biomarkers to a high degree. The test is adaptable to a wide population and it is possible that machine-learning can be applied to make the diagnostic process quicker and smoother.