MALAT-1, a novel noncoding RNA, and thymosin beta4 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 beta4 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 beta4 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.

• Authors: 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
• Journal: Oncogene (Oncogene) Vol. 22 Issue 39 Pg. 8031-41 (Sep 11 2003) ISSN: 0950-9232 [Print] England
• PMID: 12970751 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Untranslated
• thymosin beta(4)
• Thymosin

Topics

• Carcinoma, Non-Small-Cell Lung (genetics, mortality, pathology, surgery)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Humans
• In Situ Hybridization (methods)
• Lung Neoplasms (genetics, mortality, pathology, surgery)
• Molecular Sequence Data
• Neoplasm Metastasis (genetics)
• Neoplasm Staging
• Predictive Value of Tests
• RNA, Untranslated
• Reference Values
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Thymosin (genetics)