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Related Experiment Video

Updated: Jun 22, 2026

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
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Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and

Qing-Hai Ye1, Lun-Xiu Qin, Marshonna Forgues

  • 1Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.

Nature Medicine
|March 18, 2003
PubMed
Summary

Hepatocellular carcinoma (HCC) metastasis is driven by primary tumor gene expression. Osteopontin is a key driver, serving as a diagnostic marker and therapeutic target for metastatic HCC.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with high mortality.
  • Intra-hepatic metastasis is a primary cause of HCC-related deaths.

Purpose of the Study:

  • To identify a molecular signature for classifying metastatic HCC patients.
  • To discover genes associated with metastasis and patient survival in HCC.
  • To evaluate osteopontin as a diagnostic and therapeutic target for metastatic HCC.

Main Methods:

  • Analysis of gene expression profiles in HCC samples with and without intra-hepatic metastases.
  • Application of a supervised machine-learning algorithm to identify a molecular signature.
  • In vitro and in vivo experiments using osteopontin-specific antibodies.

Main Results:

  • A novel molecular signature capable of classifying metastatic HCC patients was developed.
  • Gene expression in primary tumors correlated with their corresponding metastases, indicating early initiation of metastatic potential.
  • Osteopontin was identified as a key gene, over-expressed in metastatic HCC.
  • Osteopontin inhibition reduced HCC cell invasion and pulmonary metastasis in vivo.

Conclusions:

  • Metastasis-driving genes are initiated in primary HCC tumors.
  • Osteopontin is a promising diagnostic marker and therapeutic target for metastatic HCC.