Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer.

Florian Weiland,Martin K Oehler,Karin Sundfeldt,Manuela Klingler-Hoffmann,Andrew N Stephens,Peter Hoffmann,Noor A Lokman,Thomas Jobling

doi:10.3389/fonc.2020.01767

Abstract

Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted. We performed intraoperative blood sampling from ovarian veins of stage I epithelial ovarian carcinomas and analyzed the serum proteome. Junction plakoglobin (JUP) was found to be elevated in venous blood from ovaries with malignancies when compared to those with benign disease. Peripheral plasma JUP levels were validated by ELISA in a multicenter international patient cohort. JUP was significantly increased in FIGO serous stage IA+B (1.97-fold increase; p < 0.001; n = 20), serous stage I (2.09-fold increase; p < 0.0001; n = 40), serous stage II (1.81-fold increase, p < 0.001, n = 23) and serous stage III ovarian carcinomas (1.98-fold increase; p < 0.0001; n = 34) vs. normal controls (n = 109). JUP plasma levels were not increased in early stage breast cancer (p = 0.122; n = 12). In serous ovarian cancer patients, JUP had a sensitivity of 85% in stage IA+B and 60% in stage IA-C, with specificities of 76 and 94%, respectively. A logistic regression model of JUP and Cancer Antigen 125 (CA125) revealed a sensitivity of 70% for stage IA+B and 75% for stage IA-C serous carcinomas at 100% specificity. Our novel ovarian blood sampling – proteomics approach identified JUP as a promising new biomarker for epithelial ovarian cancer, which in combination with CA125 might fulfill the test criteria for ovarian cancer screening.

Highlights

Ovarian cancer (OC) accounts for an estimated 239,000 new cases and 152,000 deaths worldwide each year [1]
To overcome the challenges of OC biomarker detection, we developed a novel approach of combining: (a) Ovarian blood sampling, to obtain blood with higher biomarker concentration downstream of the cancer, with (b) Abundance protein depletion and saturation labeling 2D-DIGE, to identify less abundant proteins in plasma and serum
Proteins that are over-expressed by cancer cells and released into the bloodstream remain the ideal markers for early detection

Summary

Introduction

Ovarian cancer (OC) accounts for an estimated 239,000 new cases and 152,000 deaths worldwide each year [1]. The high mortality rate of ovarian cancer arises due to the asymptomatic progression of the disease, resulting in over 70% of cases being diagnosed at advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III and IV] when the cancer has spread. Detection of OC at an early stage, i.e., when it is still confined to the ovary (FIGO stage I), is associated with a 5-year survival rate of over 90% compared to

Methods

Results

Conclusion