title: 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.affiliation: Department of Medicine, University of Münster, Germany.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
authors.forename: Wenbing
authors.initials: W
authors.lastname: Wang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böing
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Nicola
authors.initials: N
authors.lastname: Tidow
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brandt
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
authors.forename: Etmar
authors.initials: E
authors.lastname: Bulk
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D022661:RNA, Untranslated; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013947:Thymosin / Q000235:genetics*; D000099201:Thymosin beta(4)
chemical_list: D022661:RNA, Untranslated; D013947:Thymosin; D000099201:Thymosin beta(4)