Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning

Qing Hai Ye, Lun Xiu Qin, Marshonna Forgues, Ping He, Jin Woo Kim, Amy C. Peng, Richard Simon, Yan Li, Ana I. Robles, Yidong Chen, Zeng Chen Ma, Zhi Quan Wu, Sheng Long Ye, Yin Kun Liu, Zhao You Tang, Xin Wei Wang

Research output: Contribution to journalArticlepeer-review

662 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. We analyzed the expression profiles of HCC samples without or with intra-hepatic metastases. Using a supervised machine-learning algorithm, we generated for the first time a molecular signature that can classify metastatic HCC patients and identified genes that were relevant to metastasis and patient survival. We found that the gene expression signature of primary HCCs with accompanying metastasis was very similar to that of their corresponding metastases, implying that genes favoring metastasis progression were initiated in the primary tumors. Osteopontin, which was identified as a lead gene in the signature, was over-expressed in metastatic HCC; an osteopontin-specific antibody effectively blocked HCC cell invasion in vitro and inhibited pulmonary metastasis of HCC cells in nude mice. Thus, osteopontin acts as both a diagnostic marker and a potential therapeutic target for metastatic HCC.

Original languageEnglish (US)
Pages (from-to)416-423
Number of pages8
JournalNature Medicine
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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