Testing for Multiple Biomarkers at a Time Can Increase Early Detection of OC

Testing for additional biomarkers along with the well-known biomarker CA125 can improve the detection of early-stage ovarian cancer, a new study shows. The blood-based assay could significantly improve patient survival if ovarian cancers are identified earlier.

The study, “Simultaneous Measurement of 92 Serum Protein Biomarkers for the Development of a Multi-Protein Classifier for Ovarian Cancer Detection,” was published in the journal Cancer Prevention Research.

Ovarian cancer is the one of the leading causes of cancer-related death in women around the world, mostly because women are diagnosed at later stages, when the chances of cure are low.

“In the earliest stages, ovarian cancer can be treated with a 5-year survival rate of more than 90%. However, in later stages, the 5-year survival rate decreases to about 30%,” Amy P.N. Skubitz, PhD, researcher at the University of Minnesota, said in an interview with Healio HemOnc Today.

There is currently no accurate test to screen for ovarian cancer in the general population.

Two ovarian cancer biomarkers — CA125 and HE4 — can help monitor recurrence of ovarian cancer. However, neither can adequately detect ovarian cancer when used alone for early-stage disease.

Therefore, researchers set out to test whether a combination of proteins could improve the diagnostic accuracy for early ovarian cancer.

To identify potential new biomarkers, the researchers used Proseek Multiplex Oncology II plates,  a platform that can simultaneously measure the levels of 92 cancer-related proteins using the serum (a component of blood) of patients.

Then, using serum from 61 women with high-grade ovarian cancer, researchers compared the expression of these 92 cancer-related proteins to 88 age-matched healthy women.

Computer analysis was able to separate ovarian cancer patients from healthy women using data from the plates, thus indicating that the protein expression is different and sufficient to differentiate between the two groups.

Next, researchers showed that data from the Proseek plates for CA125 levels was strongly correlated with clinical values for CA125, thereby indicating that the technology is comparable to validated tests.

Specifically, there were 52 proteins whose expression was significantly different between ovarian cancer patients and healthy subjects. Twelve of these proteins, including CA125 and HE4, were significantly higher in patients with ovarian cancer compared to healthy individuals.

While the 92 proteins were chosen for their known roles in cancer, four of these 12 proteins are potentially novel ovarian cancer biomarkers, which had never been identified as elevated in these patients.

The researchers found a total combination of 40 proteins that have potential to serve as biomarkers for ovarian cancer, but they also found that combining CA125 with five additional biomarkers provided the best results in identifying early ovarian cancer.

Given the low prevalence of the disease, researchers estimate that a screening test must achieve a minimum specificity (i.e. the probability that a healthy serum sample will be
identified correctly) of 75% and a sensitivity (i.e. the probability that an ovarian cancer sample will be identified correctly) superior to 99.6%.

While CA125 measurements alone achieved a sensitivity of 85% at the required specificity of 99.6%, the addition these five additional proteins — FGFBP1, S100A4, EGF, ICOSLG, and MSLN — led to a sensitivity of 95.1% at a specificity of 99.6%.

This “increase in sensitivity would have a significant effect on the number of women correctly identified when screening a large population,” the researchers said.

“If the blood-based test is ultimately proven effective, women at high risk for ovarian cancer, as well as women in the general population, could be tested on an annual basis for levels of these proteins in their blood. Women would ultimately be able to find out if they had early-stage ovarian cancer. This would result in better survival rates,” Skubitz said.