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

Ping Ji, Sven Diederichs, Wenbing Wang, Sebastian Böing, Ralf Metzger, Paul M. Schneider, Nicola Tidow, Burkhard Brandt, Horst Buerger, Etmar Bulk, Michael Thomas, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow

Research output: Contribution to journalArticle

1344 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8031-8041
Number of pages11
JournalOncogene
Volume22
Issue number39
DOIs
StatePublished - Sep 11 2003
Externally publishedYes

    Fingerprint

Keywords

  • MALAT-1
  • Metastasis
  • Non-small cell lung cancer
  • Prognostic parameter
  • Subtractive hybridization
  • Thymosin β4

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Ji, P., Diederichs, S., Wang, W., Böing, S., Metzger, R., Schneider, P. M., Tidow, N., Brandt, B., Buerger, H., Bulk, E., Thomas, M., Berdel, W. E., Serve, H., & Müller-Tidow, C. (2003). MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22(39), 8031-8041. https://doi.org/10.1038/sj.onc.1206928