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  • Oncogenomics
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Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection

Abstract

To characterize molecular mechanism involved in pancreatic carcinogenesis, we analysed gene-expression profiles of 18 pancreatic tumors using a cDNA microarray representing 23 040 genes. As pancreatic ductal adenocarcinomas usually contain a low proportion of cancer cells in the tumor mass, we prepared 95% pure populations of pancreatic cancer cells by means of laser microbeam microdissection, and compared their expression profiles to those of similarly purified, normal pancreatic ductal cells. We identified 260 genes that were commonly upregulated and 346 genes that were downregulated in pancreatic cancer cells. Because of the high degree of purity in the cell populations, a large proportion of genes that we detected as upregulated or downregulated in pancreatic cancers were different from those reported in previous studies. Comparison of clinicopathological parameters with the expression profiles indicated that altered expression of 76 genes was associated with lymph-node metastasis and that of 168 genes with liver metastasis. In addition, expression levels of 30 genes were related to the recurrence of disease. These genome-wide expression profiles should provide useful information for finding candidate genes whose products might serve as specific tumor markers and/or as molecular targets for treatment of patients with pancreatic cancer.

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References

  • Bockman DE, Boydston WR and Parsa I . (1983). Gastroenterology, 85, 55–61.

  • Brentnall TA, Bronner MP, Byrd DR, Haggitt RC and Kimmey MB . (1999). Ann. Intern. Med., 131, 247–255.

  • Chambers SK, Kacinski BM, Ivins CM and Carcangiu ML . (1997). Clin. Cancer Res., 3, 999–1007.

  • Ciardiello F and Tortora G . (2001). Clin. Cancer Res., 7, 2958–2970.

  • Crnogorac-Jurcevic T, Efthimiou E, Nielsen T, Loader J, Terris B, Stamp G, Baron A, Scarpa A and Lemoine NR . (2002). Oncogene, 21, 4587–4594.

  • DiMagno EP, Reber HA and Tempero MA . (1999). Gastroenterology, 117, 1464–1484.

  • Fang G, Kim CN, Perkins CL, Ramadevi N, Winton E, Wittmann S and Bhalla KN . (2000). Blood, 96, 2246–2253.

  • Gianni L . (2002). Oncology, 63 (Suppl 1), 47–56.

  • Gjerdrum LM, Lielpetere I, Rasmussen LM, Bendix K and Hamilton-Dutoit S . (2001). J. Mol. Diagn., 3, 105–110.

  • Goggins M, Hruban RH and Kern SE . (2000). Am. J. Pathol., 156, 1767–1771.

  • Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomeld CD and Lander ES . (1999). Science, 286, 531–537.

  • Greenlee RT, Hill-tHarmon MB, Murray T and Thun M . (2001). CA Cancer J. Clin., 51, 15–36.

  • Guo H, Li R, Zucker S and Toole BP . (2000). Cancer Res., 60, 888–891.

  • Han H, Bearss DJ, Browne LW, Calaluce R, Nagle RB and Von Hoff DD . (2002). Cancer Res., 62, 2890–2896.

  • Hao D and Rowinsky EK . (2002). Cancer Invest., 20, 387–404.

  • Hruban RH, Wilentz RE and Kern SE . (2000). Am. J. Pathol., 156, 1821–1825.

  • Iacobuzio-Donahue CA, Maitra A, Shen-Ong GL, van Heek T, Ashfaq R, Meyer R, Walter K, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE, Goggins M and Hruban RH . (2002). Am. J. Pathol., 160, 1239–1249.

  • Ishiguro H, Shimokawa T, Tsunoda T, Tanaka T, Fujii Y, Nakamura Y and Furukawa Y . (2002). Oncogene, 21, 6387–6394.

  • Ishiguro H, Tsunoda T, Tanaka T, Fujii Y, Nakamura Y and Furukawa Y . (2001). Oncogene, 20, 5062–5066.

  • Kitahara O, Furukawa Y, Tanaka T, Kihara C, Ono K, Yanagawa R, Nita ME, Takagi T, Nakamura Y and Tsunoda T . (2001). Cancer Res., 61, 3544–3549.

  • Klejman A, Rushen L, Morrione A, Slupianek A and Skorski T . (2002). Oncogene, 21, 5868–5876.

  • Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A and Wils J . (1999). Ann. Surg., 230, 776–784.

  • Laheru D, Biedrzycki B and Jaffee EM . (2001). Cancer J., 7, 324–337.

  • Logsdon CD, Simeone DM, Binkley C, Arumugam T, Greenson JK, Giordano TJ, Misek DE and Hanash S . (2003). Cancer Res., 63, 2649–2657.

  • Maney T, Hunter AW, Wagenbach M and Wordeman L . (1998). J. Cell Biol., 142, 787–801.

  • Ng IO, Liang ZD, Cao L and Lee TK . (2000). Cancer Res., 60, 6581–6584.

  • Okamura S, Arakawa H, Tanaka T, Nakanishi H, Ng CC, Taya Y, Monden M and Nakamura Y . (2001). Mol. Cell, 8, 85–94.

  • Ono K, Tanaka T, Tsunoda T, Kitahara O, Kihara C, Okamoto A, Ochiai K, Takagi T and Nakamura Y . (2000). Cancer Res., 60, 5007–5011.

  • Rehwald U, Schulz H, Reiser M, Sieber M, Staak JO, Morschhauser F, Driessen C, Rudiger T, Muller-Hermelink K, Diehl V and Engert A . (2003). Blood, 101, 420–424.

  • Rosenberg L . (2000). Drugs, 59, 1071–1089.

  • Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, Goodman SN, Sohn TA, Hruban RH, Yeo CJ and Kern SE . (1997). Cancer Res., 57, 1731–1734.

  • Saito-Hisaminato A, Katagiri T, Kakiuchi S, Nakamura T, Tsunoda T and Nakamura Y . (2002). DNA Res., 9, 35–45.

  • Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y and Nakamura Y . (2000). Nat. Genet., 24, 245–250.

  • Scanlan MJ, Welt S, Gordon CM, Chen YT, Gure AO, Stockert E, Jungbluth AA, Ritter G, Jager D, Jager E, Knuth A and Old LJ . (2002). Cancer Res., 62, 4041–4047.

  • Shaw LM, Rabinovitz I, Wang HH, Toker A and Mercurio AM . (1997). Cell, 91, 949–960.

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J and Norton L . (2001). N. Engl. J. Med., 344, 783–792.

  • Sperti C, Pasquali C, Piccoli A and Pedrazzoli S . (1997). World J.Surg., 21, 195–200.

  • Violette S, Festor E, Pandrea-Vasile I, Mitchell V, Adida C, Dussaulx E, Lacorte JM, Chambaz J, Lacasa M and Lesuffleur T . (2003). Int. J. Cancer, 103, 185–193.

  • Yagyu R, Hamamoto R, Furukawa Y, Okabe H, Yamamura T and Nakamura Y . (2002). Int. J. Oncol., 20, 1173–1178.

  • Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS and Popescu NC . (1998). Cancer Res., 58, 2196–2199.

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Acknowledgements

We thank Hiroko Bando, Noriko Sudo, Kie Naito, Saori Osawa, and Miwako Ando for fabrication of the cDNA microarray; Emi Ichihashi for analysis of the data; Tae Makino for preparation of samples by cryostat; Drs Minoru Takada, Katsuhiko Murakawa, Eiji Tamoto, and Manabu Shindo for preparation of surgical specimens; Drs Tatsuya Kato, Toshihiko Nishidate, and Keisuke Taniuchi for experiment of LMM and semi-quantitative RT–PCR; Dr Naoki Oyaizu for pathological advice; and Drs Hitoshi Zembutsu, Takefumi Kikuchi, Satoshi Nagayama, and Soji Kakiuchi for helpful discussions. This work was supported in part by Research for the Future Program Grant #00L01402 from the Japan Society for the Promotion of Science.

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Correspondence to Yusuke Nakamura.

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Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Nakamura, T., Furukawa, Y., Nakagawa, H. et al. Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection. Oncogene 23, 2385–2400 (2004). https://doi.org/10.1038/sj.onc.1207392

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