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》

作者：

邢戌健 , 賈戶亮 , 張磊 , 葉青海

復旦大學附屬中山醫院、肝癌研究所（上海200032）;

關鍵詞：

肝細胞癌基因芯片診斷指標

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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，尋找與肝細胞癌發生、發展相關的基因。基因芯片由美國國立衛生院癌癥研究所制定，每張芯片有9 984個點，含9 180個基因。基因芯片實驗采用雙色熒光直接標記法，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，發現有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生、發展過程中也發揮非常重要的作用。
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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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.

《中國普外基礎與臨床雜志》

基因芯片技術在肝細胞癌候選診斷指標篩選中的應用

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《中國普外基礎與臨床雜志》

基因芯片技術在肝細胞癌候選診斷指標篩選中的應用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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