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MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer


Early-stage non-small cell lung cancer (NSCLC) can be cured by surgical resection, but a substantial fraction of patients ultimately dies due to distant metastasis. In this study, we used subtractive hybridization to identify gene expression differences in stage I NSCLC tumors that either did or did not metastasize in the course of disease. Individual clones (n=225) were sequenced and quantitative RT–PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin β4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients (n=70). The genes’ association with metastasis was stage- and histology specific. The Kaplan–Meier analyses identified MALAT-1 and thymosin β4 as prognostic parameters for patient survival in stage I NSCLC. The novel MALAT-1 transcript is a noncoding RNA of more than 8000 nt expressed from chromosome 11q13. It is highly expressed in lung, pancreas and other healthy organs as well as in NSCLC. MALAT-1 expressed sequences are conserved across several species indicating its potentially important function. Taken together, these data contribute to the identification of early-stage NSCLC patients that are at high risk to develop metastasis. The identification of MALAT-1 emphasizes the potential role of noncoding RNAs in human cancer.

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  • Bekri S, Adelaide J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pebusque MJ, Theillet C, Birnbaum and Gaudray P . (1997). Cytogenet. Cell Genet., 79, 125–131.

  • 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.

  • Brem R, Hildebrandt T, Jarsch M, Van Muijen GN and Weidle UH . (2001). Anticancer Res., 21, 1731–1740.

  • Chakrabarti R, Srivatsan ES, Wood TF, Eubanks PJ, Ebrahimi SA, Gatti RA, Passaro Jr E and Sawicki MP . (1998). Genes Chromosomes Cancer, 22, 130–137.

  • Chenchik A, Zhu YY, Diatchenko L, Li R, Hill J and Siebert PD . (1998). Gene Cloning and Analysis by RT–PCR. BioTechniques Books: Natick, MA, pp. 305–319.

    Google Scholar 

  • Clark EA, Golub TR, Lander ES and Hynes RO . (2000). Nature, 406, 532–535.

  • FANTOM and RIKEN . (2002). Nature, 420, 563–573.

  • Fidler IJ . (1990). Cancer Res., 50, 6130–6138.

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

  • Gingras AC, Raught B and Sonenberg N . (1999). Annu. Rev. Biochem., 68, 913–963.

  • Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, Kester MB, Kim YS, Wang Y, Emmert-Buck MR, Liotta LA, Spiegel AM, Boguski MS, Roe BA, Collins FS, Marx SJ, Burns L and Chandrasekharappa SC . (1997). Genome Res., 7, 725–735.

  • Hesketh R . (1997). The Oncogene and Tumour Suppressor Gene FactsBook, 2nd edn. Academic Press, Harcourt Brace & Company: New York.

    Google Scholar 

  • Hibi K, Liu Q, Beaudry GA, Madden SL, Westra WH, Wehage SL, Yang SC, Heitmiller RF, Bertelsen AH, Sidransky D and Jen J . (1998). Cancer Res., 58, 5690–5694.

  • Horak ER, Leek R, Klenk N, LeJeune S, Smith K, Stuart N, Greenall M, Stepniewska K and Harris AL . (1992). Lancet, 340, 1120–1124.

  • James MR, Richard III CW, Schott JJ, Yousry C, Clark K, Bell J, Terwilliger JD, Hazan J, Dubay C and Vignal A ., et al, (1994). Nat. Genet., 8, 70–76.

  • Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB and Johnson DH . (2000). N. Engl. J. Med., 343, 1217–1222.

  • Kikuchi T, Daigo Y, Katagiri T, Tsunoda T, Okada K, Kakiuchi S, Zembutsu H, Furukawa Y, Kawamura M, Kobayashi K, Imai K and Nakamura Y . (2003). Oncogene, 22, 2192–2205.

  • Kobayashi T, Okada F, Fujii N, Tomita N, Ito S, Tazawa H, Aoyama T, Choi SK, Shibata T, Fujita H and Hosokawa M . (2002). Am. J. Pathol., 160, 869–882.

  • Li X, Zimmerman A, Copeland NG, Gilbert DJ, Jenkins NA and Yin HL . (1996). Genomics, 32, 388–394.

  • Lu Z, Jiang G, Blume-Jensen P and Hunter T . (2001). Mol. Cell. Biol., 21, 4016–4031.

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

  • Müller-Tidow C, Metzger R, Kügler K, Diederichs S, Idos G, Thomas M, Dockhorn-Dworniczak B, Schneider PM, Koeffler HP, Berdel WE and Serve H . (2001). Cancer Res., 61, 647–653.

  • Nagamachi Y, Tani M, Shimizu K, Tsuda H, Niitsu Y and Yokota J . (1998). Cancer Lett., 127, 203–209.

  • Parker SL, Tong T, Bolden S and Wingo PA . (1997). CA Cancer J. Clin., 47, 5–27.

  • Rasio D, Negrini M, Manenti G, Dragani TA and Croce CM . (1995). Cancer Res., 55, 3988–3991.

  • Ridley A . (2000). Nature, 406, 466–467.

  • Shieh DB, Godleski J, Herndon II JE, Azuma T, Mercer H, Sugarbaker DJ and Kwiatkowski DJ . (1999). Cancer, 85, 47–57.

  • Shimizu K, Nagamachi Y, Tani M, Kimura K, Shiroishi T, Wakana S and Yokota J . (2000). Genomics, 65, 113–120.

  • Sorenson S, Glimelius B and Nygren P . (2001). Acta Oncol., 40, 327–339.

  • Souquet PJ and Geriniere L . (2001). Lung Cancer, 34 (Suppl 2), S155–S158.

  • Ukena D . (2001). Lung Cancer, 33 (Suppl 1), S25–S28.

  • Ura H, Bonfil RD, Reich R, Reddel R, Pfeifer A, Harris CC and Klein-Szanto AJ . (1989). Cancer Res., 49, 4615–4621.

  • van Asseldonk M, Schepens M, de Bruijn D, Janssen B, Merkx G and Geurts van Kessel A . (2000). Genomics, 66, 35–42.

  • Weston WM, LeClair EE, Trzyna W, McHugh KM, Nugent P, Lafferty CM, Ma L, Tuan RS and Greene RM . (1999). J. Biol. Chem., 274, 13698–13703.

  • Xu G, Rong T and Lin P . (2000). Chin. Med. J. (Engl), 113, 617–620.

  • Zimmer SG, DeBenedetti A and Graff JR . (2000). Anticancer Res., 20, 1343–1351.

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We thank Sarah Pierschalski for excellent technical assistance. The sequences of MALAT-1 have been deposited into GenBank (long isoform: Acc# BK001418, short isoform: Acc♯ BK001411).

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Correspondence to Carsten Müller-Tidow.

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This work is supported by a grant from the Wilhelm Sander-Stiftung (2001.086.1)

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Ji, P., Diederichs, S., Wang, W. et al. MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22, 8031–8041 (2003).

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  • metastasis
  • non-small cell lung cancer
  • subtractive hybridization
  • prognostic parameter
  • thymosin β4
  • MALAT-1

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