Prediagnostic plasma proteomics profile for hepatocellular carcinoma.
J Natl Cancer Inst
; 116(8): 1343-1355, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-38688524
ABSTRACT
OBJECTIVE:
Proteomics may discover pathophysiological changes related to hepatocellular carcinoma, an aggressive and lethal type of cancer with low sensitivity for early stage diagnosis.DESIGN:
We measured 1305 prediagnostic (median = 12.7 years) SomaScan proteins from 54 pairs of healthy individuals who subsequently developed hepatocellular carcinoma and matched non-hepatocellular carcinoma control individuals from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Candidate proteins were validated in the independent, prospective UK Biobank Pharma Proteomics Project (UKB-PPP).RESULTS:
In NHS and HPFS, we identified 56 elevated proteins in hepatocellular carcinoma with an absolute fold change of more than 1.2 and a Wald test P value less than .05 in conditional logistic regression analysis. Ingenuity pathway analysis identified enrichment of pathways associated with cell viability, adhesion, proteolysis, apoptosis, and inflammatory response. Four proteins-chitinase-3-like protein 1, growth differentiation factor 15, interleukin-1 receptor antagonist protein, and E-selectin-showed strong positive associations with hepatocellular carcinoma and were thus validated by enzyme-linked immunosorbent assay (odds ratio = 2.48-14.7, all P < .05) in the NHS and HPFS and by Olink platform (hazard ratio = 1.90-3.93, all P < .05) in the UKB-PPP. Adding these 4 proteins to a logistic regression model of traditional hepatocellular carcinoma risk factors increased the area under the curve from 0.67 to 0.87 in the NHS and HPFS. Consistently, model area under the curve was 0.88 for hepatocellular carcinoma risk prediction in the UKB-PPP.CONCLUSION:
However, the limited number of hepatocellular carcinoma patients in the cohorts necessitates caution in interpreting our findings, emphasizing the need for further validation in high-risk populations.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
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Carcinoma Hepatocelular
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Proteómica
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Neoplasias Hepáticas
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
J Natl Cancer Inst
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos