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Updated: May 10, 2025
Preparation of Mitochondria from Ovarian Cancer Tissues and Control Ovarian Tissues for Quantitative Proteomics Analysis
Published on: November 18, 2019
Serum metabolic fingerprints encode functional biomarkers for ovarian cancer diagnosis: a large-scale cohort study
Wanshan Liu1, Xiaoxiao Hu2, Zhouzhou Bao2
1Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; State Key Laboratory for Oncogenes and Related Genes, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, School of Biomedical Engineering, Institute of Medical Robotics and Shanghai Academy of Experimental Medicine, Shanghai Jiao Tong University, Shanghai 200030, PR China; Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
Background:
Ovarian cancer (OC) ranks as the most lethal gynaecological malignancy worldwide, with early diagnosis being crucial yet challenging. Current diagnostic methods like transvaginal ultrasound and blood biomarkers show limited sensitivity/specificity. This study aimed to identify and validate serum metabolic biomarkers for OC diagnosis using the largest cohort reported to date.
Methods:
We constructed a large-scale OC-associated cohort of 1432 subjects, including 662 OC, 563 benign ovarian disease, and 207 healthy control subjects, across retrospective (n = 1073) and set-aside validation (n = 359) cohorts. Serum metabolic fingerprints (SMFs) were recorded using nanoparticle-enhanced laser desorption/ionization mass spectrometry (NELDI-MS). A diagnostic panel was developed through machine learning of SMFs in the discovery cohort and validated in independent verification and set-aside validation cohorts. The identified metabolic biomarkers were further validated using liquid chromatography MS and their biological functions were assessed in OC cell lines.
Findings:
We identified a metabolic biomarker panel including glucose, histidine, pyrrole-2-carboxylic acid, and dihydrothymine. This panel achieved consistent areas under the curve (AUCs) of 0.87-0.89 for distinguishing between malignant and benign ovarian masses across all cohorts, and improved to AUCs of 0.95-0.99 when combined with risk of ovarian malignancy algorithm (ROMA). In vitro validation provided initial biological context for the metabolic alterations observed in our diagnostic panel.
Interpretation:
Our study established a reliable serum metabolic biomarker panel for OC diagnosis with potential clinical translations. The NELDI-MS based approach offers advantages of fast analytical speed (∼30 s/sample) and low cost (∼2-3 dollars/sample), making it suitable for large-scale clinical applications.
Funding:
MOST (2021YFA0910100), NSFC (82421001, 823B2050, 824B2059, and 82173077), Medical-Engineering Joint Funds of Shanghai Jiao Tong University (YG2021GD02, YG2024ZD07, and YG2023ZD08), Shanghai Science and Technology Committee Project (23JC1403000), Shanghai Institutions of Higher Learning (2021-01-07-00-02-E00083), Shanghai Jiao Tong University Inner Mongolia Research Institute (2022XYJG0001-01-16), Sichuan Provincial Department of Science and Technology (2024YFHZ0176), Innovation Research Plan by the Shanghai Municipal Education Commission (ZXWF082101), Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20210700), Basic-Clinical Collaborative Innovation Project from Shanghai Immune Therapy Institute, Guangdong Basic and Applied Basic Research Foundation (2024A1515013255).
