A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma

Chanhee Han, Stefania Bellone, Eric R. Siegel, Gary Altwerger, Gulden Menderes, Elena Bonazzoli, Tomomi Egawa-Takata, Francesca Pettinella, Anna Bianchi, Francesco Riccio, Luca Zammataro, Ghanshyam Yadav, Jarrod A. Marto, Marie-France Penet, Douglas A. Levine, Ronny Drapkin, Abhijit Patel, Babak Litkouhi, Elena Ratner, Dan Arin Silasi & 4 others Gloria S. Huang, Masoud Azodi, Peter E. Schwartz, Alessandro D. Santin

Research output: Contribution to journalArticle

Abstract

Introduction: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. Methods: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. Results: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC = 0.961) performed better than CA 125 alone (AUC = 0.851; P = 0.0150) and HE4 alone (AUC = 0.870; P = 0.0220), but also performed significantly better than the 2- marker combination of CA125 + HE4 (AUC = 0.922; P = 0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. Conclusion: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Area Under Curve
ROC Curve
Biomarkers
Carcinoma
Ovarian Neoplasms
Interleukin-6
Interleukin 1 Receptor Antagonist Protein
Validation Studies
Early Detection of Cancer
Immunoassay
Adenocarcinoma
Multivariate Analysis
Pathology
Gene Expression
Sensitivity and Specificity
Antibodies
Serum
Neoplasms

Keywords

  • Biomarkers
  • Early detection
  • Ovarian cancer
  • Serous ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Han, C., Bellone, S., Siegel, E. R., Altwerger, G., Menderes, G., Bonazzoli, E., ... Santin, A. D. (Accepted/In press). A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology. https://doi.org/10.1016/j.ygyno.2018.03.050

A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. / Han, Chanhee; Bellone, Stefania; Siegel, Eric R.; Altwerger, Gary; Menderes, Gulden; Bonazzoli, Elena; Egawa-Takata, Tomomi; Pettinella, Francesca; Bianchi, Anna; Riccio, Francesco; Zammataro, Luca; Yadav, Ghanshyam; Marto, Jarrod A.; Penet, Marie-France; Levine, Douglas A.; Drapkin, Ronny; Patel, Abhijit; Litkouhi, Babak; Ratner, Elena; Silasi, Dan Arin; Huang, Gloria S.; Azodi, Masoud; Schwartz, Peter E.; Santin, Alessandro D.

In: Gynecologic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Han, C, Bellone, S, Siegel, ER, Altwerger, G, Menderes, G, Bonazzoli, E, Egawa-Takata, T, Pettinella, F, Bianchi, A, Riccio, F, Zammataro, L, Yadav, G, Marto, JA, Penet, M-F, Levine, DA, Drapkin, R, Patel, A, Litkouhi, B, Ratner, E, Silasi, DA, Huang, GS, Azodi, M, Schwartz, PE & Santin, AD 2018, 'A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma', Gynecologic Oncology. https://doi.org/10.1016/j.ygyno.2018.03.050
Han, Chanhee ; Bellone, Stefania ; Siegel, Eric R. ; Altwerger, Gary ; Menderes, Gulden ; Bonazzoli, Elena ; Egawa-Takata, Tomomi ; Pettinella, Francesca ; Bianchi, Anna ; Riccio, Francesco ; Zammataro, Luca ; Yadav, Ghanshyam ; Marto, Jarrod A. ; Penet, Marie-France ; Levine, Douglas A. ; Drapkin, Ronny ; Patel, Abhijit ; Litkouhi, Babak ; Ratner, Elena ; Silasi, Dan Arin ; Huang, Gloria S. ; Azodi, Masoud ; Schwartz, Peter E. ; Santin, Alessandro D. / A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. In: Gynecologic Oncology. 2018.
@article{b5b07edc77f444da9512b4db333cb140,
title = "A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma",
abstract = "Introduction: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. Methods: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. Results: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC = 0.961) performed better than CA 125 alone (AUC = 0.851; P = 0.0150) and HE4 alone (AUC = 0.870; P = 0.0220), but also performed significantly better than the 2- marker combination of CA125 + HE4 (AUC = 0.922; P = 0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100{\%} down to ~95{\%}. Conclusion: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.",
keywords = "Biomarkers, Early detection, Ovarian cancer, Serous ovarian cancer",
author = "Chanhee Han and Stefania Bellone and Siegel, {Eric R.} and Gary Altwerger and Gulden Menderes and Elena Bonazzoli and Tomomi Egawa-Takata and Francesca Pettinella and Anna Bianchi and Francesco Riccio and Luca Zammataro and Ghanshyam Yadav and Marto, {Jarrod A.} and Marie-France Penet and Levine, {Douglas A.} and Ronny Drapkin and Abhijit Patel and Babak Litkouhi and Elena Ratner and Silasi, {Dan Arin} and Huang, {Gloria S.} and Masoud Azodi and Schwartz, {Peter E.} and Santin, {Alessandro D.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ygyno.2018.03.050",
language = "English (US)",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma

AU - Han, Chanhee

AU - Bellone, Stefania

AU - Siegel, Eric R.

AU - Altwerger, Gary

AU - Menderes, Gulden

AU - Bonazzoli, Elena

AU - Egawa-Takata, Tomomi

AU - Pettinella, Francesca

AU - Bianchi, Anna

AU - Riccio, Francesco

AU - Zammataro, Luca

AU - Yadav, Ghanshyam

AU - Marto, Jarrod A.

AU - Penet, Marie-France

AU - Levine, Douglas A.

AU - Drapkin, Ronny

AU - Patel, Abhijit

AU - Litkouhi, Babak

AU - Ratner, Elena

AU - Silasi, Dan Arin

AU - Huang, Gloria S.

AU - Azodi, Masoud

AU - Schwartz, Peter E.

AU - Santin, Alessandro D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. Methods: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. Results: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC = 0.961) performed better than CA 125 alone (AUC = 0.851; P = 0.0150) and HE4 alone (AUC = 0.870; P = 0.0220), but also performed significantly better than the 2- marker combination of CA125 + HE4 (AUC = 0.922; P = 0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. Conclusion: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.

AB - Introduction: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. Methods: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. Results: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC = 0.961) performed better than CA 125 alone (AUC = 0.851; P = 0.0150) and HE4 alone (AUC = 0.870; P = 0.0220), but also performed significantly better than the 2- marker combination of CA125 + HE4 (AUC = 0.922; P = 0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. Conclusion: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.

KW - Biomarkers

KW - Early detection

KW - Ovarian cancer

KW - Serous ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=85044144508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044144508&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2018.03.050

DO - 10.1016/j.ygyno.2018.03.050

M3 - Article

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

ER -