Abstract DPOC-011: A MULTIPLEX PLATFORM FOR THE IDENTIFICATION OF SERUM BIOMARKERS FOR THE EARLY DETECTION OF OVARIAN CANCER
Authors: Boylan Kristin L.M. , Geschwind Kate , Koopmeiners Joseph S. , Geller Melissa A. , Skubitz Amy P.N. 
Published: June 2017

PURPOSE. Early detection is the key to increased survival of ovarian cancer patients, however, a screening tool that is adequately sensitive and specific for use in the general population has yet to be developed. CA125 and HE4 are two biomarkers that are currently approved by the FDA for monitoring recurrence of ovarian cancer. We hypothesize that by simultaneously screening dozens of cancer–related biomarkers for their levels of expression in serum samples in a standardized multiplex assay, we will be able to develop an algorithm to screen for early stages of ovarian cancer.

EXPERIMENTAL PROCEDURES. In this project, we used a multiplex approach to identify candidate biomarkers for early stages of ovarian cancer. We used a Proseek® Multiplex Oncology I plate (Olink Bioscience) to analyze the expression of 92 biomarkers (including CA125 and HE4) in one microliter of serum collected from 22 women in each of four groups: healthy, benign ovarian tumors, early stage I/II serous ovarian cancer, and late stage III/IV serous ovarian cancer. Biomarker levels were simultaneously quantified based on the Proximity Extension Assay. This innovative technology combines the sensitivity of the polymerase chain reaction with the specificity of antibody–based detection methods, allowing multiplex biomarker detection and high throughput quantification.

SUMMARY OF THE DATA. We found that CA125 and HE4 were present at very low levels in healthy controls and the benign cases, while higher levels were found in the early stage cases, and the highest levels of CA125 and HE4 were found in the late stage cases. Overall, statistically significant trends were observed for 37 of the 92 markers (i.e. p &lt; 0.001), many of which have yet to be documented as candidate serum biomarkers for ovarian cancer. The CA125 data from the Proseek® plate exhibited a strong correlation with the CA125 values obtained by ELISA which were abstracted from the patients' medical records, with a Pearson's correlation coefficient of 0.84 (95% CI: 0.76, 0.89). In spite of the small sample size (22 cases each for early stage ovarian cancer vs. healthy), the area under the ROC curve (AUC) for CA125 was determined to be 0.98 (95% CI: 0.95, 1.0) and the AUC for HE4 was determined to be 0.84 (95% CI: 0.71, 0.95). In total, 22 biomarkers had an estimated AUC greater than 0.7, when comparing early stage ovarian cancer vs. healthy, and were significantly associated with cancer status, thus motivating further investigation.

CONCLUSIONS. These data provide proof–of–principle that the Proseek® technology can replicate the results of conventional ELISAs for these known oncology biomarkers. In future studies, we plan to use a larger sample size in order to refine our model and validate our results. Our ultimate goal is to develop an algorithm of biomarkers that can be used to screen women for early stages of ovarian cancer, when the likelihood of long term survival is greatest.

Citation Format: Kristin L.M. Boylan, Kate Geschwind, Joseph S. Koopmeiners, Melissa A. Geller, and Amy P.N. Skubitz. A MULTIPLEX PLATFORM FOR THE IDENTIFICATION OF SERUM BIOMARKERS FOR THE EARLY DETECTION OF OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-011.