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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

Abstract

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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Acknowledgements

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). https://doi.org/10.1038/sj.onc.1206928

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Keywords

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

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