Identification of Candidate Diagnostic Tumor Markers for Human Hepatocellular Carcinoma Using Genechip Technology_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XING Xujian , JIA Huliang , ZHANG Lei , YE Qinghai

Liver Cancer Institute and Zhongshan Hospital， Fudan University， Shanghai 200032， China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Genechip; Diagnostic marker

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Objective 　To identify genes associated with hepatocellular carcinoma (HCC) as candidate diagnostic markers in a genome-wide scale.
Methods 　The gene expression profiles of 40 pairs of HCC tumor tissue and peripheral non-tumorous liver tissue were analyzed by using gene chip technology.The gene chips were fabricated at the National Cancer Institute (NCI). Each gene chip contained 9 180 genes. The fluorescent targets were prepared by a direct labeling approach using two kinds of fluorescences as following: 100 μg of total RNA from non-cancerous liver tissue was labeled with Cy3-dUTP and 200 μg of total RNA from HCC was labeled with Cy5-dUTP. The targets were mixed together and hybridized with genes on the gene chips. Unsupervised hierarchical clustering analysis was done by CLUSTER and TREEVIEW software using median centered correlation and complete linkage.
Results 　A total of 10 genes were found up-regulated in over 80% of primary tumors comparing with that of their corresponding non-tumorous liver tissues at a two-fold filter
with an unsupervised hierarchical clustering algorithm, including protocadherin-alpha 9, ESTs, Homo sapiens cDNA FLJ, KPNA2, RPS20, SNRPE, CDKN2A, UBD, MDK and ANXA2.
Conclusion 　These genes are supposed to be candidates for the diagnosis of HCC. Further investigation of these genes in a large scale of patients with HCC and patients with non-malignant hepatic diseases will be needed to disclose whether they could be used clinically as novel diagnostic tumor markers for HCC.

Citation： XING Xujian,JIA Huliang,ZHANG Lei,YE Qinghai. Identification of Candidate Diagnostic Tumor Markers for Human Hepatocellular Carcinoma Using Genechip Technology. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(1): 23-27. doi: Copy

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1. 　Parkin DM, Bray F, Ferlay J, et al. Estimating the world cancer burden: Globocan 2000 [J]. Int J Cancer， 2001; 94(2)∶153.
2. 　Zhou XD, Tang ZY, Yang BH, et al. Experience of 1 000 patients who underwent hepatectomy for small hepatocellular carcinoma [J]. Cancer， 2001; 91(8)∶1479.
3. 　Taketa K. Alpha-fetoprotein: reevaluation in hepatology [J]. Hepatology， 1990; 12(6)∶1420.
4. 　Mackay A, Jones C, Dexter T, et al. cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells [J]. Oncogene， 2003; 22(17)∶2680.
5. 　Taniwaki M, Daigo Y, Ishikawa N, et al. Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer [J]. Int J Oncol， 2006; 29(3)∶567.
6. 　Welsh JB, Zarrinkar PP, Sapinoso LM, et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer [J]. Proc Natl Acad Sci USA， 2001; 98(3)∶1176.
7. 　Young AN, Amin MB, Moreno CS, et al. Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers [J]. Am J Pathol， 2001; 158(5)∶1639.
8. 　Hegde P, Qi R, Gaspard R, et al. Identification of tumor ma-rkers in models of human colorectal cancer using a 19,200-element complementary DNA microarray [J]. Cancer Res， 2001; 61(21)∶7792.
9. 　Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, et al. Disc-overy of novel tumor markers of pancreatic cancer using global gene expression technology [J]. Am J Pathol， 2002; 160(4)∶1239.
10. 　Xiao SY, Wang HL, Hart J, et al. cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma [J]. Am J Pathol， 2001; 159(4)∶1415.
11. 　Pergolizzi JV Jr, Auster M, Conaway GL, et al. Cryosurgery for unresectable primary hepatocellular carcinoma: a case report and review of literature [J]. Am Surg， 1999; 65(5)∶402.
12. 　Nobata S, Shinozawa T, Sakanishi A. Truncated midkine induces transformation of cultured cells and short latency of tumorigenesis in nude mice [J]. Cancer Lett， 2005; 219(1)∶83.
13. 　Koide N, Hada H, Shinji T, et al. Expression of the midkine gene in human hepatocellular carcinomas [J]. Hepatogastroenterology， 1999; 46(30)∶3189.
14. 　Ikematsu S, Yano A, Aridome K, et al. Serum midkine levels are increased in patients with various types of carcinomas [J]. Br J Cancer， 2000; 83(6)∶701.
15. 　Ikematsu S, Okamoto K, Yoshida Y, et al. High levels of urinary midkine in various cancer patients [J]. Biochem Biophys Res Commun， 2003; 306(2)∶329.
16. 　Filipenko NR, MacLeod TJ, Yoon CS, et al. Annexin A2 is a novel RNA-binding protein [J]. J Biol Chem， 2004; 279(10)∶8723.
17. 　Laumonnier Y, Syrovets T, Burysek L, et al. Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes [J]. Blood， 2006; 107(8)∶3342.
18. 　Gillette JM, Chan DC, Nielsen-Preiss SM. Annexin 2 expression is reduced in human osteosarcoma metastases [J]. J Cell Biochem， 2004; 92(4)∶820.
19. 　Tatenhorst L, Rescher U, Gerke V, et al. Knockdown of annexin 2 decreases migration of human glioma cells in vitro [J]. Neuropathol Appl Neurobiol， 2006; 32(3)∶271.
20. 　Yoon SY, Kim JM, Oh JH, et al. Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags [J]. Int J Oncol， 2006; 29(2)∶315.
21. 　Dorr SN, Schlicker MN, Hansmann IN. Genomic structure of karyopherin alpha 2 (KPNA2) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndrome [J]. Hum Genet， 2001; 109(5)∶479.
22. 　Teng SC, Wu KJ, Tseng SF, et al. Importin KPNA2, NBS1, DNA Repair and Tumorigenesis [J]. J Mol Histol， 2006; [Epub ahead of print].
23. 　Dahl E, Kristiansen G, Gottlob K, et al. Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha 2 as a potential novel prognostic marker in breast cancer [J]. Clin Cancer Res， 2006; 12(13)∶3950.
24. 　Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome [J]. J Natl Cancer Inst， 2006; 98(7)∶472.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Identification of Candidate Diagnostic Tumor Markers for Human Hepatocellular Carcinoma Using Genechip Technology

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