Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Christopher M Tarney; Guisong Wang; Nicholas W Bateman; Kelly A Conrads; Ming Zhou; Brian L Hood; Jeremy Loffredo; Chunqiao Tian; Kathleen M Darcy; Chad A Hamilton; Yovanni Casablanca; Anna Lokshin; Thomas P Conrads; G Larry Maxwell

doi:10.1016/j.ajog.2019.06.005

Biomarker panel for early detection of endometrial cancer in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Am J Obstet Gynecol. 2019 Nov;221(5):472.e1-472.e10. doi: 10.1016/j.ajog.2019.06.005. Epub 2019 Jul 4.

Affiliations

¹ Department of Obstetrics and Gynecology, Gynecologic Cancer Center of Excellence, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD.
² Department of Obstetrics and Gynecology, Gynecologic Cancer Center of Excellence, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD.
³ Department of Obstetrics and Gynecology, Gynecologic Cancer Center of Excellence, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA.
⁴ University of Pittsburgh Medical Center, Pittsburgh, PA.
⁵ Department of Obstetrics and Gynecology, Gynecologic Cancer Center of Excellence, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA; Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA. Electronic address: thomas.conrads@inova.org.
⁶ Department of Obstetrics and Gynecology, Gynecologic Cancer Center of Excellence, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD; Inova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, VA; Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA. Electronic address: george.maxwell@inova.org.

PMID: 31279844
DOI: 10.1016/j.ajog.2019.06.005

Abstract

Background: Endometrial cancer is the most common gynecological cancer in the United States. However, no early detection test exists for asymptomatic women at average risk for endometrial cancer.

Objective: We sought to identify early detection biomarkers for endometrial cancer using prediagnostic serum.

Study design: We performed a nested case-control study of postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (n = 78,216), including 112 incident endometrial cancer cases and 112 controls. Prediagnostic serum was immunodepleted of high-abundance proteins and digested with sequencing grade porcine trypsin via pressure cycling technology. Quantitative proteomics and phosphoproteomics was performed using high-resolution liquid chromatography-tandem mass spectrometry and highly multiplexed isobaric mass tag combined with basic reversed-phase liquid chromatography. A set of proteins able to predict cancer status was identified with an integrated score assessed by receiver-operator curve analysis.

Results: Mean time from blood draw to endometrial cancer diagnosis was 3.5 years (SD, 1.9 years). There were 47 differentially abundant proteins between cases and controls (P < .05). Protein alterations with high predictive potential were selected by regression analysis and compiled into an aggregate score to determine the ability to predict endometrial cancer. An integrated risk score of 6 proteins was directly related to disease incidence in cases with blood draw ≤2 years, >2 years to ≤5 years or >5 years prior to cancer diagnosis. The integrated score distinguished cases from controls with an area under the curve of 0.80 (95% confidence interval, 0.72-0.88).

Conclusion: An integrated score of 6 proteins using prediagnostic serum from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial distinguishes postmenopausal endometrial cancer cases from controls. Validation is needed to evaluate whether this test can improve prediction or detection of endometrial cancer among postmenopausal women.

Keywords: biomarkers; early detection; endometrial cancer; prediagnostic serum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers, Tumor / blood*
Cadherins / blood
Case-Control Studies
Catalase / blood
Chromatography, Liquid
Complement Factor B / analysis
Early Detection of Cancer*
Endometrial Neoplasms / blood
Endometrial Neoplasms / diagnosis*
Endometrial Neoplasms / epidemiology
Female
Humans
Middle Aged
Proteasome Endopeptidase Complex / blood
Proteomics
Protocadherins
Randomized Controlled Trials as Topic
Sensitivity and Specificity
Tandem Mass Spectrometry
Transferrin / analysis
beta 2-Microglobulin / blood

Substances

B2M protein, human
Biomarkers, Tumor
Cadherins
PCDH18 protein, human
Protocadherins
Transferrin
beta 2-Microglobulin
Catalase
Complement Factor B
Proteasome Endopeptidase Complex