Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient\u2019s plasma \u2013 a prospective trial

A Hasenburg,D Eichkorn,M Bossart,A Geroldinger,R Zeillinger,F Vosshagen,E Obermayr

doi:10.1186/s12885-021-08682-y

Abstract

BackgroundTrial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors.MethodsIn this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses.ResultsPlasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor.ConclusionsThe calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort.Trial registrationClinical Trials.gov under NCT01763125, registered Jan. 8, 2013.

Highlights

Trial on five plasma biomarkers (CA125, Human epididymis 4 (HE4), OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors
A good screening program for the early detection of ovarian cancer or its precursors and the presurgical differentiation between benign and malignant ovarian masses seen in transvaginal ultrasound (TVUS) is sought-after
cancer antigen 125 (CA125) In the single protein analysis CA125 achieved an Area under the Curve (AUC) of 0.929

Summary

Introduction

Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. 20% of patients are diagnosed at stage I and II because of missing screening strategies [2]. The combination of transvaginal ultrasound (TVUS) and laboratory test for cancer antigen 125 (CA125) in patient plasma for the early detection of ovarian cancer did not improve survival rates [3, 4]. A good screening program for the early detection of ovarian cancer or its precursors and the presurgical differentiation between benign and malignant ovarian masses seen in TVUS is sought-after. The International Ovarian Tumour Analysis Group (IOTA) published ten criteria which have shown high reliability in clinical diagnosis using TVUS for the differentiation between malignant and benign ovarian masses [7]. The IOTA prediction models showed excellent diagnostic performance with an Area under the Curve (AUC) of 0.96 and 0.95 [8]

Methods

Results

Conclusion