Identify metastasis-associated genes in hepatocellular carcinoma through clonality delineation for multinodular tumor

• Published in: Cancer research (Chicago, Ill.) Ill.), 2002-08, Vol.62 (16), p.4711-4721
• Main Authors: SIU TIM CHEUNG, XIN CHEN, XIN YUAN GUAN, SAN YU WONG, LAI SHAN TAI, O. L. NG, Irene, SO, Samuel, SHEUNG TAT FAN
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - secondary; Chromosome Aberrations; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling; Genes, p53; Hepatitis B virus - genetics; Humans; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Mutation; Neoplasm Staging; Nucleic Acid Hybridization - methods; Oligonucleotide Array Sequence Analysis; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; Tumors; Virus Integration
• ISSN: 0008-5472; 1538-7445

Disease recurrence and metastasis are frequently observed in many successfullytreated localized cancers, including hepatocellular carcinoma in which intrahepatic and extrahepatic recurrence (metastasis) are frequently observed after curative resection. The present study aimed at identifying metastasis-associated genes through delineation of the clonality for multinodular liver cancer. The clonal relationship of 22 tumor foci from six patients was investigated by the genome-wide expression profile via cDNA microarray consisting of 23,000 genes. Tumor molecular properties including p53 protein overexpression and gene mutation, hepatitis B virus integration pattern, and genetic alteration examined by comparative genomic hybridization were compared. Results indicated that gene expression patterns could serve as the molecular fingerprint for clonality identification. Together with the molecular data from p53, hepatitis B virus integration and comparative genomic hybridization profiles, tumor nodules from five patients were confirmed with clonal relationship, and the expression profiles of the primary nodules were compared with their corresponding intrahepatic metastatic nodules. A total of 90 clones were found to be correlated with intrahepatic metastasis by Student's t test (P < 0.05). With reference to the primary tumor, 63 clones (39 known genes and 24 express sequence tags) were down-regulated whereas 27 clones (14 known genes and 13 express sequence tags) were up-regulated in the metastatic nodules. These metastasis-associated genes may provide clues to reveal patients with increased risk of developing metastasis, and to identify novel therapeutic targets for the treatment of metastasis.