Gene Set: LEE_LIVER_CANCER

Standard name LEE_LIVER_CANCER
Systematic name M3879
Brief description Genes down-regulated in tumor compared to non-tumor liver samples from patients with hepatocellular carcinoma (HCC).
Full description or abstract We searched for potential suppressors of tumor metastasis by identifying the genes that are frequently down-regulated in hepatocellular carcinomas (HCC) while being negatively correlated with clinical parameters relevant to tumor metastasis, and we report here on the identification of N-myc downstream regulated gene 2 (NDRG2) as a promising candidate. NDRG2 expression was significantly reduced in HCC compared with nontumor or normal liver tissues [87.5% (35 of 40) and 62% (62 of 100) at RNA and protein levels, respectively]. Reduction of NDRG2 expression was intimately associated with promoter hypermethylation because its promoter region was found to carry extensively methylated CpG sites in HCC cell lines and primary tumors. Immunohistochemical analysis of NDRG2 protein in 100 HCC patient tissues indicated that NDRG2 expression loss is significantly correlated with aggressive tumor behaviors such as late tumor-node-metastasis (TNM) stage (P = 0.012), differentiation grade (P = 0.024), portal vein thrombi (P = 0.011), infiltrative growth pattern (P = 0.015), nodal/distant metastasis (P = 0.027), and recurrent tumor (P = 0.021), as well as shorter patient survival rates. Ectopically expressed NDRG2 suppressed invasion and migration of a highly invasive cell line, SK-Hep-1, and experimental tumor metastasis in vivo, whereas small interfering RNA-mediated knockdown resulted in increased invasion and migration of a weakly invasive cell line, PLC/PRF/5. In addition, NDRG2 could antagonize transforming growth factor beta1-mediated tumor cell invasion by specifically down-regulating the expression of matrix metalloproteinase 2 and laminin 332 pathway components, with concomitant suppression of Rho GTPase activity. These results suggest that NDRG2 can inhibit extracellular matrix-based, Rho-driven tumor cell invasion and migration and thereby play important roles in suppressing tumor metastasis in HCC.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18519680   Authors: Lee DC,Kang YK,Kim WH,Jang YJ,Kim DJ,Park IY,Sohn BH,Sohn HA,Lee HG,Lim JS,Kim JW,Song EY,Kim DM,Lee MN,Oh GT,Kim SJ,Park KC,Yoo HS,Choi JY,Yeom YI
Exact source Table 2S
Related gene sets (show 13 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Leona Saunders (Broad Institute)
Source platform UnigeneIdentifiers
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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