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Comparison of gene expression in hepatocellular carcinoma, liver development, and liver regeneration

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Abstract

Proliferation of liver cells can be observed in hepatocarcinogenesis, at different stages of liver development, and during liver regeneration after an injury. Does it imply that they share similar molecular mechanisms? Here, the transcriptional profiles of hepatocellular carcinoma (HCC), liver development, and liver regeneration were systematically compared as a preliminary attempt to answer this question. From the comparison, we found that advanced HCC mimics early development in terms of deprived normal liver functions and activated cellular proliferation, but advanced HCC and early development differ in expressions of cancer-related genes and their transcriptional controls. HCC and liver regeneration demonstrate different expression patterns as a whole, but regeneration is similar to dysplasia (pre-stage of HCC) in terms of their proximity to the normal state. In summary, of these three important processes, the carcinogenic progress carries the highest variance in expression; HCC pre-stage shares some resemblance with liver regeneration; and advanced HCC stage displays similarity with early development.

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References

  • Arai K, Takano S, Teratani T, Ito Y, Yamada T, Nozawa R (2008) S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Targets 8:243–252

    Article  CAS  PubMed  Google Scholar 

  • Castillo-Davis CI, Hartl DL (2003) GeneMerge—post-genomic analysis, data mining, and hypothesis testing. Bioinformatics 19:891–892

    Article  CAS  PubMed  Google Scholar 

  • Coulouarn C, Derambure C, Lefebvre G, Daveau R, Hiron M, Scotte M, Francois A, Daveau M, Salier JP (2005) Global gene repression in hepatocellular carcinoma and fetal liver, and suppression of dudulin-2 mRNA as a possible marker for the cirrhosis-to-tumor transition. J Hepatol 42:860–869

    Article  CAS  PubMed  Google Scholar 

  • Dai M, Wang P, Boyd AD et al (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res 33:e175

    Article  PubMed  Google Scholar 

  • Damdinsuren B, Nagano H, Kondo M et al (2005) Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation. Int J Oncol 26:319–327

    CAS  PubMed  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868

    Article  CAS  PubMed  Google Scholar 

  • Hermani A, Hess J, De Servi B, Medunjanin S, Grobholz R, Trojan L, Angel P, Mayer D (2005) Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res 11:5146–5152

    Article  CAS  PubMed  Google Scholar 

  • Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    Article  PubMed  Google Scholar 

  • Jin H, Pan Y, He L et al (2007) p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer. Mol Cancer Res 5:423–433

    Article  CAS  PubMed  Google Scholar 

  • Kaiser S, Park YK, Franklin JL et al (2007) Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol 8:R131

    Article  PubMed  Google Scholar 

  • Kelley-Loughnane N, Sabla GE, Ley-Ebert C, Aronow BJ, Bezerra JA (2002) Independent and overlapping transcriptional activation during liver development and regeneration in mice. Hepatology 35:525–534

    Article  CAS  PubMed  Google Scholar 

  • Krones-Herzig A, Adamson E, Mercola D (2003) Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence. Proc Natl Acad Sci USA 100:3233–3238

    Article  CAS  PubMed  Google Scholar 

  • Krones-Herzig A, Mittal S, Yule K, Liang H, English C, Urcis R, Soni T, Adamson ED, Mercola D (2005) Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res 65:5133–5143

    Article  CAS  PubMed  Google Scholar 

  • Leukert N, Vogl T, Strupat K, Reichelt R, Sorg C, Roth J (2006) Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity. J Mol Biol 359:961–972

    Article  CAS  PubMed  Google Scholar 

  • Li T, Huang J, Jiang Y, Zeng Y, He F, Zhang MQ, Han Z, Zhang X (2009) Multi-stage analysis of gene expression and transcription regulation in C57/B6 mouse liver development. Genomics 93:235–242

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Cai Z, Galson DL, Xiao G, Liu Y, George DE, Melhem MF, Yao Z, Zhang J (2006) Monocyte chemotactic protein-1 (MCP-1) acts as a paracrine and autocrine factor for prostate cancer growth and invasion. Prostate 66:1311–1318

    Article  CAS  PubMed  Google Scholar 

  • Mahner S, Baasch C, Schwarz J, Hein S, Wolber L, Janicke F, Milde-Langosch K (2008) C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma. Br J Cancer 99:1269–1275

    Article  CAS  PubMed  Google Scholar 

  • Matys V, Fricke E, Geffers R et al (2003) TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 31:374–378

    Article  CAS  PubMed  Google Scholar 

  • Moon A, Yong HY, Song JI et al (2008) Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res 6:1544–1553

    Article  CAS  PubMed  Google Scholar 

  • Naxerova K, Bult CJ, Peaston A, Fancher K, Knowles BB, Kasif S, Kohane IS (2008) Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Genome Biol 9:R108

    Article  PubMed  Google Scholar 

  • Noetzel E, Veeck J, Niederacher D, Galm O, Horn F, Hartmann A, Knuchel R, Dahl E (2008) Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer. BMC Cancer 8:154

    Article  PubMed  Google Scholar 

  • Otu HH, Naxerova K, Ho K, Can H, Nesbitt N, Libermann TA, Karp SJ (2007) Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns. J Biol Chem 282:11197–11204

    Article  CAS  PubMed  Google Scholar 

  • Pelicano H, Lu W, Zhou Y, Zhang W, Chen Z, Hu Y, Huang P (2009) Mitochondrial dysfunction and reactive oxygen species imbalance promote breast cancer cell motility through a CXCL14-mediated mechanism. Cancer Res 69:2375–2383

    Article  CAS  PubMed  Google Scholar 

  • Pouliot F, Blais A, Labrie C (2003) Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells. Cancer Res 63:277–281

    CAS  PubMed  Google Scholar 

  • Roth J, Vogl T, Sorg C, Sunderkotter C (2003) Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol 24:155–158

    Article  CAS  PubMed  Google Scholar 

  • Salomaki HH, Sainio AO, Soderstrom M, Pakkanen S, Laine J, Jarvelainen HT (2008) Differential expression of decorin by human malignant and benign vascular tumors. J Histochem Cytochem 56:639–646

    Article  CAS  PubMed  Google Scholar 

  • Sandelin A, Alkema W, Engstrom P, Wasserman WW, Lenhard B (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res 32:D91–D94

    Article  CAS  PubMed  Google Scholar 

  • Seidler DG, Goldoni S, Agnew C, Cardi C, Thakur ML, Owens RT, McQuillan DJ, Iozzo RV (2006) Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem 281:26408–26418

    Article  CAS  PubMed  Google Scholar 

  • Smith AD, Sumazin P, Xuan Z, Zhang MQ (2006) DNA motifs in human and mouse proximal promoters predict tissue-specific expression. Proc Natl Acad Sci USA 103:6275–6280

    Article  CAS  PubMed  Google Scholar 

  • Storey JD, Xiao W, Leek JT, Tompkins RG, Davis RW (2005) Significance analysis of time course microarray experiments. Proc Natl Acad Sci USA 102:12837–12842

    Article  CAS  PubMed  Google Scholar 

  • Thorgeirsson SS, Grisham JW (2002) Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31:339–346

    Article  CAS  PubMed  Google Scholar 

  • Turovskaya O, Foell D, Sinha P et al (2008) RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 29:2035–2043

    Article  CAS  PubMed  Google Scholar 

  • Wente MN, Mayer C, Gaida MM, Michalski CW, Giese T, Bergmann F, Giese NA, Buchler MW, Friess H (2008) CXCL14 expression and potential function in pancreatic cancer. Cancer Lett 259:209–217

    Article  CAS  PubMed  Google Scholar 

  • Wurmbach E, Chen YB, Khitrov G et al (2007) Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology 45:938–947

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Xueya Zhou for helpful discussions. This work is partially supported by NSFC (30625012, 60721003, and 60905014), Tsinghua University SIST Basic Research Fund, Chinese National Key Program on Basic Research (2006CB910402), Shanghai Commission for Science and Technology (08JC14164), China Postdoctoral Science Foundation (20070420097), and Shanghai Postdoctoral Science Foundation (07R214138).

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Authors and Affiliations

  1. Department of Biomedical Informatics, Peking University Health Science Center, 38 Xueyuan Rd, Beijing, 100191, China

    Tingting Li

  2. MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing, 100084, China

    Tingting Li & Xuegong Zhang

  3. Chinese National Human Genome Center at Shanghai, 351 Guo shou-jing Road, Shanghai, 201203, China

    Bingbing Wan & Jian Huang

  4. National Engineering Center for Biochip at Shanghai, 151 Libin Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201203, China

    Jian Huang

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  1. Tingting Li
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  2. Bingbing Wan
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  3. Jian Huang
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  4. Xuegong Zhang
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Correspondence to Tingting Li.

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Communicated by S. Hohmann.

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Li, T., Wan, B., Huang, J. et al. Comparison of gene expression in hepatocellular carcinoma, liver development, and liver regeneration. Mol Genet Genomics 283, 485–492 (2010). https://doi.org/10.1007/s00438-010-0530-y

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  • DOI: https://doi.org/10.1007/s00438-010-0530-y

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