title: Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning.
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.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Amy C
authors.initials: AC
authors.lastname: Peng
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ana I
authors.initials: AI
authors.lastname: Robles
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Zeng-Chen
authors.initials: ZC
authors.lastname: Ma
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Wu
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Ye
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics* / Q000276:immunology
chemical_list: C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin