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Prediagnostic plasma proteomics profile for hepatocellular carcinoma
Xinyuan Zhang1, Longgang Zhao1,2, Long H Ngo3,4
1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Journal of the National Cancer Institute
|April 30, 2024
Summary
Proteomics identified four key proteins that significantly improve early detection of hepatocellular carcinoma (liver cancer). These biomarkers enhance risk prediction models, aiding in earlier diagnosis of this aggressive disease.
Area of Science:
- Proteomics and Cancer Biomarkers
- Hepatocellular Carcinoma (HCC) Pathophysiology
- Early Cancer Detection Strategies
Background:
- Hepatocellular carcinoma (HCC) is an aggressive cancer with poor early diagnosis sensitivity.
- Proteomic analysis offers potential for discovering pathophysiological changes linked to HCC.
- Identifying reliable biomarkers is crucial for improving HCC detection and patient outcomes.
Purpose of the Study:
- To identify prediagnostic proteomic biomarkers for hepatocellular carcinoma (HCC) using a large-scale proteomic approach.
- To validate candidate HCC biomarkers in independent prospective cohorts.
- To assess the utility of identified biomarkers in improving HCC risk prediction models.
Main Methods:
- SomaScan proteomic analysis of 1305 proteins in prediagnostic plasma samples from 54 pairs of individuals who developed HCC and matched controls (Nurses' Health Study and Health Professionals Follow-up Study).
- Validation of candidate proteins using enzyme-linked immunosorbent assay (ELISA) and Olink platform in independent prospective cohorts (UK Biobank Pharma Proteomics Project).
- Logistic regression and conditional logistic regression analyses were used to identify and validate HCC-associated proteins and assess model performance.
Main Results:
- Fifty-six proteins were found to be elevated in prediagnostic samples of individuals who later developed HCC.
- Four proteins (chitinase-3-like protein 1, growth differentiation factor 15, interleukin-1 receptor antagonist protein, and E-selectin) showed strong positive associations with HCC.
- Incorporating these four proteins into risk models significantly increased the area under the curve (AUC) for HCC prediction, from 0.67 to 0.87/0.88.
Conclusions:
- The identified four proteins serve as promising prediagnostic biomarkers for hepatocellular carcinoma (HCC).
- These biomarkers substantially enhance the predictive accuracy of HCC risk models.
- Further validation in high-risk populations is recommended due to the limited number of HCC cases in the initial cohorts.
