A Blood-Based Metabolite Panel for Distinguishing Ovarian Cancer from Benign Pelvic Masses

Authors

Ehsan Irajizad
Chae Y Han
Joseph Celestino
Ranran Wu
Eunice Murage
Rachelle Spencer
Jennifer B Dennison
Jody Vykoukal
James P Long
Kim Anh Do
Charles Drescher
Karen Lu
Zhen Lu
Robert C Bast
Sam Hanash
Johannes F Fahrmann

Publication Date

11-1-2022

Journal

Clinical Cancer Research

Abstract

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts.

EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an independent set of sera from 118 ovarian cancer cases and 56 subjects with BPM. The contributions of the panel for improving upon the performance of ROMA were further assessed.

RESULTS: A 7-marker metabolite panel (7MetP) developed in the training set yielded an AUC of 0.86 [95% confidence interval (CI): 0.76-0.95] for early-stage ovarian cancer in the independent test set. The 7MetP+ROMA model had an AUC of 0.93 (95% CI: 0.84-0.98) for early-stage ovarian cancer in the test set, which was improved compared with ROMA alone [0.91 (95% CI: 0.84-0.98); likelihood ratio test P: 0.03]. In the entire specimen set, the combined 7MetP+ROMA model yielded a higher positive predictive value (0.68 vs. 0.52; one-sided P < 0.001) with improved specificity (0.89 vs. 0.78; one-sided P < 0.001) for early-stage ovarian cancer compared with ROMA alone.

CONCLUSIONS: A blood-based metabolite panel was developed that demonstrates independent predictive ability and complements ROMA for distinguishing early-stage ovarian cancer from benign disease to better inform clinical decision making.

Keywords

Female, Humans, CA-125 Antigen, WAP Four-Disulfide Core Domain Protein 2, Neoplasms, Glandular and Epithelial, Proteins, Carcinoma, Ovarian Epithelial, Ovarian Neoplasms, Biomarkers, Tumor, Algorithms

Comments

Supplementary Materials

PMID: 36037307