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A multigene expression panel for the molecular diagnosis of Barrett's esophagus and Barrett's adenocarcinoma of the esophagus

Oncogene volume 23, pages 4780–4788 (2004)Cite this article

Abstract

In order to identify genes or combination of genes that have the power to discriminate between premalignant Barrett's esophagus and Barrett's associated adenocarcinoma, we analysed a panel of 23 genes using quantitative real-time RT–PCR (qRT–PCR, Taqman®) and bioinformatic tools. The genes chosen were either known to be associated with Barrett's carcinogenesis or were filtered from a previous cDNA microarray study on Barrett's adenocarcinoma. A total of 98 tissues, obtained from 19 patients with Barrett's esophagus (BE group) and 20 patients with Barrett's associated esophageal adenocarcinoma (EA group), were studied. Triplicate analysis for the full 23 gene of interest panel, and analysis of an internal control gene, was performed for all samples, for a total of more than 9016 single PCR reactions. We found distinct classes of gene expression patterns in the different types of tissues. The most informative genes clustered in six different classes and had significantly different expression levels in Barrett's esophagus tissues compared to adenocarcinoma tissues. Linear discriminant analysis (LDA) distinguished four genetically different groups. The normal squamous esophagus tissues from patients with BE or EA were not distinguishable from one another, but Barrett's esophagus tissues could be distinguished from adenocarcinoma tissues. Using the most informative genes, obtained from a logistic regression analysis, we were able to completely distinguish between benign Barrett's and Barrett's adenocarcinomas. This study provides the first non-array parallel mRNA quantitation analysis of a panel of genes in the Barrett's esophagus model of multistage carcinogenesis. Our results suggest that mRNA expression quantitation of a panel of genes can discriminate between premalignant and malignant Barrett's disease. Logistic regression and LDAs can be used to further identify, from the complete panel, gene subsets with the power to make these diagnostic distinctions. Expression analysis of a limited number of highly selected genes may have clinical usefulness for the treatment of patients with this disease.

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References

  • Brabender J, Danenberg KD, Metzger R, Schneider PM, Lord RV, Groshen S, Tsao-Wei DD, Park J, Salonga D, Holscher AH and Danenberg PV . (2002a). Clin. Cancer Res., 8, 438–443.

  • Brabender J, Lord RV, Danenberg KD, Metzger R, Schneider PM, Park JM, Salonga D, Groshen S, Tsao-Wei DD, DeMeester TR, Holscher AH and Danenberg PV . (2001a). J. Surg. Res., 99, 301–306.

  • Brabender J, Lord RV, Danenberg KD, Metzger R, Schneider PM, Uetake H, Kawakami K, Park JM, Salonga D, Peters JH, DeMeester TR and Danenberg PV . (2001b). J. Gastrointest. Surg., 5, 174–182.

  • Brabender J, Lord RV, Metzger R, Park J, Salonga D, Danenberg KD, Danenberg PV, Holscher AH and Schneider PM . (2003). Br. J. Cancer, 89, 1508–1512.

  • Brabender J, Lord RV, Wickramasinghe K, Metzger R, Schneider PM, Park JM, Holscher AH, DeMeester TR, Danenberg KD and Danenberg PV . (2002b). J. Gastrointest. Surg., 6, 359–367.

  • Chomczynski P and Sacchi N . (1987). Anal. Biochem., 162, 156–159.

  • Cohen O and Kimchi A . (2001). Cell. Death Differ., 8, 6–15.

  • Devesa SS, Blot WJ and Fraumeni JF . (1998). Cancer, 83, 2049–2053.

  • Dudoit S, Fridlyand J and Speed T . (2002). J. Am. Stat. Assoc., 8, 77–87.

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV and Laird PW . (1999). Cancer Res., 59, 2302–2306.

  • Gibson UE, Heid CA and Williams PM . (1996). Genome Res., 6, 995–1001.

  • Heid CA, Stevens J, Livak KL and Williams PM . (1996). Genome Res., 6, 986–994.

  • Jemal A, Thomas A, Murray T and Thun M . (2002). CA Cancer J. Clin., 52, 23–47.

  • Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu CR, Peterson C and Meltzer PS . (2001). Nat. Med., 7, 673–679.

  • Lord RV, Salonga D, Danenberg KD, Peters JH, DeMeester TR, Park JM, Johansson J, Skinner KA, Chandrasoma P, DeMeester SR, Bremner CG, Tsai PI and Danenberg PV . (2000). J. Gastrointest. Surg., 4, 135–142.

  • Lord RV, Tsai PI, Danenberg KD, Peters JH, DeMeester TR, Tsao-Wei DD, Groshen S, Salonga D, Park JM, Crookes PF, Kiyabu M, Chandrasoma P and Danenberg PV . (2001). Surgery, 129, 267–276.

  • Perou CM, Sorlie T, Eisen MB, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale Al, Brown PO and Botstein D . (2000). Nature, 406, 747–752.

  • Scherf U, Williams AJ, Boland JF, Lord RV, Alvares C, Horne DT and Vockley JG . (2001). Proc. Annu. Meet. Am. Assoc. Cancer Res., 42, A3288.

  • Selaru FM, Xu Y, Yin J, Zou T, Liu TC, Mori Y, Abraham JM, Sato F, Wang S, Twigg C, Olaru A, Shustova V, Leytin A, Hytiroglou P, Shibata D, Harpaz N and Meltzer SJ . (2002a). Gastroenterology, 122, 606–613.

  • Selaru FM, Zou T, Xu Y, Shustova V, Yin J, Mori Y, Sato F, Wang S, Olaru A, Shibata D, Greenwald BD, Krasna MJ, Abraham JM and Meltzer SJ . (2002b). Oncogene, 21, 475–478.

  • Suda Y, Kuwashima Y, Tanaka Y, Uchida K, Sakamoto H, Hashiguchi Y and Sekine T . (1999). Gastric Cancer, 2, 165–172.

  • Terashima M, Irinoda T, Fujiwara H, Nakaya T, Takagane A, Abe K, Yonezawa H, Oyama K, Inaba T, Saito K, Takechi T and Fukushima M . (2002). Anticancer Res., 22, 761–768.

  • Virmani AK, Tsou J, Siegmund KD, Shen LY, Long TI, Laird PW, Gazdar AF and Laird-Offringa IA . (2002). Cancer Epidemiol. Biomark. Prev., 11, 291–297.

  • Wilson KT, Fu S, Ramanujam KS and Meltzer SJ . (1998). Cancer Res., 58, 2929–2934.

  • Woodward TA, Klingler PD, Genko PV and Wolfe JT . (2000). Anticancer Res., 20, 2427–2432.

  • Xu Y, Selaru F, Yin J, Zou TT, Shustova V, Mori Y, Sato F, Liu TC, Olaru A, Wang S, Kimos MC, Perry K, Desai K, Greenwald BD, Krasna MJ, Shibata D, Abraham JM and Meltzer SJ . (2002). Cancer Res., 62, 3493–3497.

  • Zou TT, Selaru F, Xu Y, Shustova V, Yin J, Mori Y, Shibata D, Sato F, Wang S, Olaru A, Deacu E, Liu TC, Abraham JM and Meltzer SJ . (2002). Oncogene, 21, 4855–4862.

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Acknowledgements

This work was supported in part by the Felix Burda Foundation for Cancer Research (JB), NIH grant CA 71716 (PVD), CA85069, CA01808, CA95323, CA098450, CA77057 (SJM).

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Authors and Affiliations

  1. Department of Visceral and Vascular Surgery, University of Cologne, 50931, Germany

    Jan Brabender, Ralf Metzger, Paul M Schneider & Arnulf H Hölscher

  2. Department of Preventive Medicine, University of Southern California, Los Angeles, 90033, CA, USA

    Paul Marjoram

  3. Response Genetics Inc., Los Angeles, 90033, CA, USA

    Dennis Salonga, Ji Min Park & Kathleen D Danenberg

  4. Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine and USC/Kenneth Norris Comprehensive Cancer Center, Los Angeles, 90033, CA, USA

    Sylke Schneider & Peter V Danenberg

  5. University of Maryland School of Medicine and VA Medical Center, Rm. N3W62, 22 S. Greene St, Baltimore, 21201, MD, USA

    Jing Yin & Stephen J Meltzer

  6. Department of Surgery, University of Southern California Keck School of Medicine and USC/Kenneth Norris Comprehensive Cancer Center, Los Angeles, 90033, CA, USA

    Reginald V Lord

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  1. Jan Brabender
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  2. Paul Marjoram
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  3. Dennis Salonga
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  4. Ralf Metzger
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  5. Paul M Schneider
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  6. Ji Min Park
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  7. Sylke Schneider
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  8. Arnulf H Hölscher
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  9. Jing Yin
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  11. Kathleen D Danenberg
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  12. Peter V Danenberg
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  13. Reginald V Lord
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Correspondence to Jan Brabender.

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Brabender, J., Marjoram, P., Salonga, D. et al. A multigene expression panel for the molecular diagnosis of Barrett's esophagus and Barrett's adenocarcinoma of the esophagus. Oncogene 23, 4780–4788 (2004). https://doi.org/10.1038/sj.onc.1207663

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