Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients

Leandersson, Pia LU orcid ; Åkesson, Anna LU ; Hedenfalk, Ingrid LU orcid ; Malander, Susanne LU orcid and Borgfeldt, Christer LU (2020) In PLoS ONE 15(10 October).
Abstract

Objective Survival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors. Material and methods Plasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus... (More)

Objective Survival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors. Material and methods Plasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively. Results We analyzed 177 biomarkers. Thirty-four proteins had ROC AUC > 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC > 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC > 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p < 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model). Conclusion HE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
15
issue
10 October
article number
e0240418
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:33075095
  • scopus:85093911472
ISSN
1932-6203
DOI
10.1371/journal.pone.0240418
language
English
LU publication?
yes
id
8410a2ee-fffd-480b-af9a-1721cec5710d
date added to LUP
2020-11-09 08:25:41
date last changed
2024-04-17 18:59:45
@article{8410a2ee-fffd-480b-af9a-1721cec5710d,
  abstract     = {{<p>Objective Survival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors. Material and methods Plasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively. Results We analyzed 177 biomarkers. Thirty-four proteins had ROC AUC &gt; 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC &gt; 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC &gt; 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p &lt; 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model). Conclusion HE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125.</p>}},
  author       = {{Leandersson, Pia and Åkesson, Anna and Hedenfalk, Ingrid and Malander, Susanne and Borgfeldt, Christer}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{10 October}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0240418}},
  doi          = {{10.1371/journal.pone.0240418}},
  volume       = {{15}},
  year         = {{2020}},
}