• 復旦大學附屬中山醫(yī)院、肝癌研究所（上海200032）;

目的　 在全基因組范圍內篩選肝細胞癌候選診斷指標。
方法　 采用基因芯片技術比較40例肝細胞癌腫瘤標本及其鄰近無瘤肝組織之間基因表達譜的差異，尋找與肝細胞癌發(fā)生、發(fā)展相關的基因?；蛐酒擅绹鴩⑿l(wèi)生院癌癥研究所制定，每張芯片有9 984個點，含9 180個基因?；蛐酒瑢嶒灢捎秒p色熒光直接標記法，每例患者的肝細胞癌組織總RNA 200 μg用綠色熒光素Cy5-dUTP標記，其相應的無瘤肝組織總RNA 100 μg用紅色熒光素Cy3-dUTP標記。混合后與芯片上的基因進行雜交。對基因芯片資料進行統(tǒng)計分析以尋找肝細胞癌組織與無瘤肝組織之間表達有差異的基因。
結果 　用非先導分層聚類分析法進行篩選，發(fā)現(xiàn)有10個基因在80%以上的肝細胞癌組織中的表達水平明顯高于（2倍或2倍以上）其相應的無瘤肝組織，包括ESTs、Homo sapiens cDNA FLJ、原鈣粘連素-α 9(protocadherinalpha 9)、KPNA2、RPS20、SNRPE、CDKN2A、UBD、MDK和ANXA2基因。這些基因與多種腫瘤相關，他們可能在肝細胞癌發(fā)生、發(fā)展過程中也發(fā)揮非常重要的作用。
結論 　進一步研究這些基因的功能可能篩選出新的肝細胞癌診斷指標。

引用本文： 邢戌健,賈戶亮,張磊,葉青海. 基因芯片技術在肝細胞癌候選診斷指標篩選中的應用. 中國普外基礎與臨床雜志, 2007, 14(1): 23-27. doi: 復制

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  3. 3. 　Taketa K. Alpha-fetoprotein: reevaluation in hepatology [J]. Hepatology， 1990; 12(6)∶1420.
  4. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.