The inflammatory protein interleukin-6 (IL-6) appears at significantly higher levels in the blood of ovarian cancer patients in comparison with women with benign masses in the ovaries and healthy women, new research has found.
Thus, determining IL-6 levels may supplement conventional tests and biomarker assessments used to diagnose the disease, the findings suggest.
IL-6 also may be used to distinguish people with benign tumors and normal ovaries, a setting where other diagnostic markers — like proteins CA-125 and HE4 — fall short, the investigators said.
The study, “Pre-operative sera interleukin-6 in the diagnosis of high-grade serous ovarian cancer,” was published in the journal Scientific Reports.
“Developing tests that are simpler and more practical may help get more women to hospital for treatment more effectively, with the hope that survival rates will improve,” Magdalena Plebanski, PhD, a professor at RMIT University, in Australia, and the study’s senior author, said in a press release.
Figuring out before surgery if suspicious ovarian masses are benign or malignant is a critical step in ensuring that patients receive the most appropriate care in a timely manner.
A couple of blood markers currently exist that help diagnose ovarian cancer. But they lack accuracy, are greatly affected by a women’s menopausal status, and are not very reliable in differentiating patients with malignant versus benign masses.
This led researchers to turn to inflammation markers as potential biomarkers of disease. A link between local inflammation and ovarian cancer has been described in several studies, with most ovarian cancers linked to increased amounts of pro-inflammatory proteins. Such findings led researchers to hypothesize that these markers could be measured in a woman’s blood to help diagnose the disease.
To find out, scientists at the Monash University, in Australia examined the levels of 28 inflammatory proteins in the blood of 66 women who were undergoing surgery from 2014-2016, due to suspected ovarian cancer.
Among them, 33 had advanced — stage 3-4 — ovarian cancer, 12 had a benign ovarian mass, and 21 had no ovarian growth but were undergoing risk reduction surgery due to a family history of breast or ovarian cancer or a known genetic mutation.
Only two of the 28 proteins measured — Interleukin-6 (IL-6) and IL-8 — showed significant differences in concentration between women with malignant tumors and healthy individuals (controls), and between those with benign tumors and healthy controls.
However, while IL-6 levels also were significantly different between malignant and benign masses, IL-8 was unable to distinguish between those two groups. Therefore, all three groups could be successfully identified by IL-6 levels alone.
To confirm these results, the researchers then collected blood samples from 25 ovarian cancer patients, 25 women with a benign mass, and 19 healthy volunteers. Using statistical analyses, the research team again was able to distinguish each group based on the levels of IL-6.
The usefulness of IL-6 was then compared against four additional tests, including those for CA-125 and HE-4. The other two were mathematical approaches, the Risk of Malignancy Index (RMI) and the Risk of Ovarian Malignancy Algorithm (ROMA).
Established in 1990, the RMI method for calculating risk includes a measurement of CA-125, the menopausal status of the patient, and findings from ultrasound. It is the most widely used method for assessing ovarian cancer risk. The much-newer ROMA method, designed in 2008, incorporates HE4 and CA-125 measurements, as well as menopausal status, to predict the likelihood of ovarian cancer.
All four measures do have drawbacks. CA-125 measurements can be inaccurate in pre-menopausal women, in detecting early stage cancers, and in distinguishing benign and malignant growths. HE4 and ROMA are considered more accurate, but testing for HE4 is expensive and not readily available in disadvantaged communities and in underdeveloped countries. Similarly, RMI requires ultrasound imaging, which also can be difficult to obtain in certain parts of the world.
“Our new test is as accurate as the combined results of a standard blood test and ultrasound,” Plebanski said. “This is especially important for women in remote or disadvantaged communities, where under-resourced hospitals may not have access to complex and expensive equipment like ultrasound machines or MRI scanners.”
Ultimately, the researchers concluded that IL-6 has significant predictive capabilities for ovarian cancer as a standalone test. They also indicate that testing for IL-6 could complement the results of other measures, especially when distinguishing between benign and malignant tumors.
“Patients with benign cysts identified through imaging could potentially be spared unnecessary surgeries,” Plebanski said.
One shortcoming of the study was that only patients with advanced ovarian cancer were studied, meaning that there is no data to indicate whether IL-6 is a strong indicator of early stage ovarian cancer. The researchers believe that IL-6 will still be predictive of early stage tumors, but did not have a sufficient amount of samples to investigate. Further research ultimately will be necessary to make that determination.