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  • Oncogenomics
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Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs

Oncogene volume 22, pages 2192–2205 (2003)Cite this article

Abstract

To investigate genes involved in pulmonary carcinogenesis and those related to sensitivity of nonsmall cell lung cancers (NSCLCs) to therapeutic drugs, we performed cDNA microarray analysis of 37 NSCLCs after laser-capture microdissection of cancer cells from primary tumors. A clustering algorithm applied to the expression data easily distinguished two major histological types of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. Subsequent analysis of the 18 adenocarcinomas identified 40 genes whose expression levels could separate cases with lymph-node metastasis from those without metastasis. In addition, we compared the expression data with measurements of the sensitivity of surgically dissected NSCLC specimens to six anti-cancer drugs (docetaxel, paclitaxel, irinotecan, cisplatin, gemcitabine, and vinorelbine), as measured by the CD-DST (collagen gel droplet embedded culture-drug sensitivity test) method. We found significant associations between expression levels of dozens of genes and chemosensitivity of NSCLCs. Our results provide valuable information for eventually identifying predictive markers and novel therapeutic target molecules for this type of cancer.

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Abbreviations

NSCLC:

non-small cell lung cancer

SCC:

squamous cell arcinoma

CD-DST:

collagen gel droplet embedded culture-drug sensitivity test

NESH:

NESH PROTEIN

ARHA:

ras homolog gene member A

DBI:

diazepam binding inhibitor

TACSTD1:

tumor-associated calcium signal transducer 1

DOC:

docetaxel

PAC:

paclitaxel

CPT-11:

irinotecan

CDDP:

cisplatin

GEM:

gemcitabine

NVB:

vinorelbine

CPM:

cyclophosphamide

ADR:

adriamycin

MMC:

mitomycin

T/C (%):

relative tumor volume with respect to controls

GPI:

glucose-6-phosphate isomerase

GML:

glycosylphosphatidylinositol-anchored molecule-like protein

YWHAQ:

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein

References

  • Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, lannettoni MD, Orringer MB and Hanash S . (2002). Nat Med., 8, 816–824.

  • Bhattacharjee A, Richards, WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ and Meyerson M . (2001). Proc. Natl. Acad. Sci. USA, 98, 13790–13795.

  • Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM and Deeley RG . (1992). Science, 258, 1650–1654.

  • Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR, Weiss RA and Liotta LA . (1996). Science 274, 998–1001.

  • Franklin WA, Waintrub M, Edwards D, Christensen K, Prendegrast P, Woods J, Bunn PA and Kolhouse JF . (1994). Int. J. Cancer Suppl., 8, 89–95.

  • Fukata M and Kaibuchi K . (2001). Nat. Rev. Mol. Cell Biol., 2, 887–897.

  • Furuhata T, Tokino T, Urano T and Nakamura Y . (1996). Oncogene, 13, 1965–1970.

  • Furukawa T, Kubota T and Hoffman RM . (1995). Clin. Cancer Res., 1, 305–311.

  • Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D and Petersen I . (2001). Proc. Natl. Acad. Sci. USA, 98, 13784–13789.

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

  • Ichigotani Y, Yokozaki S, Fukuda Y, Hamaguchi M and Matsuda S . (2002). Cancer Res., 62, 2215–2219.

  • Kawano N, Osawa H, Ito T, Nagashima Y, Hirahara F, Inayama Y, Nakatani Y, Kimura S, Kitajima H, Koshikawa N, Miyazaki K and Kitamura H . (1997). Hum. Pathol., 28, 613–622.

  • 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.

  • Kondoh N, Shuda M, Tanaka K, Wakatsuki T, Hada A and Yamamoto M . (2001). Anticancer Res., 21, 2429–2433.

  • Lin YM, Furukawa Y, Tsunoda T, Yue CT, Yang KC and Nakamura Y . (2002). Oncogene 21, 4120–4128.

  • Luo X, Tang Z, Rizo J and Yu H . (2002). Mol. Cell, 9, 59–71.

  • Makino K, Yu D and Hung MC . (2001). Oncogene 20, 2537–2543.

  • McDoniels-Silvers AL, Nimri CF, Stoner GD, Lubet RA and You M . (2002). Clin. Cancer Res., 8, 1127–1138.

  • Meyaard L, van der Vuurst de Vries AR, de Ruiter T, Lanier LL, Phillips JH and Clevers H . (2001). J. Exp. Med., 194, 107–112.

  • Mitsudomi T, Hamajima N, Ogawa M and Takahashi T . (2000). Clin. Cancer Res., 6, 4055–4063.

  • Niklinski J, Niklinska W, Laudanski J, Chyczewska E and Chyczewski L . (2001). Lung Cancer, 34 (Suppl 2), S53–S58.

  • Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y and Nakamura Y . (2001). Cancer Res., 61, 2129–2137.

  • Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Alien JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES and Golub TR . (2002). Nature, 415, 436–442.

  • Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, Lenz HJ, Leichman CG, Leichman L, Diasio RB and Danenberg PV . (2000). Clin. Cancer Res., 6, 1322–1327.

  • Sozzi G . (2001). Eur. J. Cancer, 37 (Suppl 7), S63–S73.

  • Turton NJ, Judah DJ, Riley J, Davies R, Lipson D, Styles JA, Smith AG and Gant TW . (2001). Oncogene, 20, 1300–1306.

  • Ueda K, Clark DP, Chen CJ, Roninson IB, Gottesman MM and Pastan I . (1987). J. Biol. Chem., 262, 505–508.

  • Vamvakopoulos NC, Modi WS and Floros J . (1995). Cytogenet. Cell. Genet., 68, 8–10.

  • van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R and Friend SH . (2002). Nature, 415, 530–536.

  • Watine J . (2000). BMJ, 320, 379–380.

  • Wieland I, Arden KC, Michels D, Klein-Hitpass L, Bohm M, Viars CS and Weidle UH . (1999). Oncogene, 18, 4530–4537.

  • Yanagawa R, Furukawa Y, Tsunoda T, Kitahara O, Kameyama M, Murata K, Ishikawa O and Nakamura Y . (2001). Neoplasia, 3, 395–401.

  • Zembutsu H, Ohnishi Y, Tsunoda T, Furukawa Y, Katagiri T, Ueyama Y, Tamaoki N, Nomura T, Kitahara O, Yanagawa R, Hirata K and Nakamura Y . (2002). Cancer Res., 62, 518–527.

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Acknowledgements

We thank Hiroko Bando, Noriko Sudo, for fabricating the cDNA microarray, Tae Makino for preparing samples of Laser Capture Microdissection, Emi Ichihashi for analysis of data, Yasuyuki Kaneta, Satoshi Nagayama, Toru Nakamura, Chie Suzuki, Nobuhisa Ishikawa, Chiyuki Furukawa, Tatsuya Kato and Yu-Min Lin for helpful discussions. This work was supported in part by a ‘Research for the Future’ Program Grant of The Japan Society for the Promotion of Science (#00L01402) to YN.

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Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Takefumi Kikuchi, Yataro Daigo, Toyomasa Katagiri, Koichi Okada, Soji Kakiuchi, Hitoshi Zembutsu, Yoichi Furukawa & Yusuke Nakamura

  2. First Department of Internal Medicine, Sapporo Medical University, Sapporo, 060-8543, Japan

    Takefumi Kikuchi & Kohzoh Imai

  3. Laboratory for Medical Informatics, SNP Research Center, Riken (Institute of Physical and Chemical Research), Kanagawa, 230-0045, Japan

    Tatsuhiko Tsunoda

  4. Division of General Thoracic Surgery, Department of Surgery, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Masafumi Kawamura & Koichi Kobayashi

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  1. Takefumi Kikuchi
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Correspondence to Yusuke Nakamura.

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Kikuchi, T., Daigo, Y., Katagiri, T. et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene 22, 2192–2205 (2003). https://doi.org/10.1038/sj.onc.1206288

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