Interleukin-6 May Reliably Identify Patients with High-Grade Serous Ovarian Cancer

February 21, 2020

A new tool, in combination with those already existing, could distinguish between patients with malignant and benign ovarian masses, as well as those with a benign ovarian mass and normal ovaries.

According to a study, published in Scientific Reports, interleukin (IL)-6 alone may be a clinically reliable biomarker to identify patients with advanced high-grade serous ovarian carcinoma and those with normal ovaries.1

Researchers also indicated that IL-6, in combination with RMI score, ROMA, HE4, or CA125, might enhance the predictive power of already existing tools or biomarkers in distinguishing between patients with malignant and benign ovarian masses, as well as those with a benign ovarian mass and normal ovaries. Moreover, patients with cysts incidentally identified on imaging could possibly be spared surgical intervention.

“Our new test is as accurate as the combined results of a standard blood test and ultrasound,” senior author and chief investigator Magdalena Plebanski, PhD, MBA, senior national health and medical research council fellow at RMIT University, said in a press release.2 “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.”

In a training cohort, researchers tested 4 existing clinical tests (RMI score and ROMA, CA125, and HE4) and a panel of 28 immune soluble biomarkers in sera from 66 patients who were set to undergo surgery for suspected ovarian cancer. Six promising immune biomarkers alone, or in combination with conventional tests, were then analyzed in an independent validation cohort (n = 69). IL-6 was recognized as the main driver of variability, followed closely by conventional diagnostic tests.

Median sera IL-6 was found to be higher in high-grade serous ovarian carcinoma, the most aggressive subtype, compared to those with a benign mass or controls with normal ovaries (28.3 vs 7.3 vs 1.2 pg/ml; < 0.0001). Additionally, the combination of IL-6 further improved the overall predictive probability of the conventional tests. 

By modelling a 2-step triage of women who had a suspicious ovarian mass, with IL-6 < 3.75 pg/ml as a primary triage followed by conventional tests (CA125 or RMI score), researchers identified ovarian cancer in patients with a misclassification rate of 4.54%-3.03%, superior to the use of CA125 or RMI alone (9.09%-10.60%). Furthermore, the validation cohort demonstrated a similar improvement in the diagnostic sensitivity following the addition of IL-6. 

“Ovarian cancer is the deadliest women’s cancer, a statistic that has not changed in 30 years,” said Plebanski. “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.”

Researchers indicated that further studies are necessary, including those that assess earlier stages of the disease, to explore and expand on the possible utility of adding IL-6 to routine diagnostic tests. 

“Given the small number of true early-stage, high-grade serous ovarian cancers available, it was necessary to make inferences using advanced disease cases,” the authors wrote. “Inclusion of early stages of epithelial ovarian cancer and comparison with benign masses and normal ovaries in a larger stage stratified cohort will be required to ascertain the role of IL-6 in generalized ovarian cancer screening including multiple and earlier disease stages.”

According to the study, although the 5-year survival rate has increased significantly, the prognosis for women with this disease type remains poor due to its late presentation and current lack of scientifically validated screening tools. 

Reference:

1. Kampan NC, Madondo MT, Reynolds J, et al. Pre-operative sera interleukin-6 in the diagnosis of high-grade serous ovarian cancer. Scientific Reports. doi:10.1038/s41598-020-59009-z.

2. Test measures immune response to improve ovarian cancer diagnosis [news release]. Published February 16, 2020. eurekalert.org/pub_releases/2020-02/ru-tmi021220.php. Accessed February 17, 2020.