MALAT-1, a novel noncoding RNA, and thymosin beta4 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 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.
Ji
Ping
P
Department of Medicine, University of Münster, Germany.
Diederichs
Sven
S
Wang
Wenbing
W
Böing
Sebastian
S
Metzger
Ralf
R
Schneider
Paul M
PM
Tidow
Nicola
N
Brandt
Burkhard
B
Buerger
Horst
H
Bulk
Etmar
E
Thomas
Michael
M
Berdel
Wolfgang E
WE
Serve
Hubert
H
Müller-Tidow
Carsten
C
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)
D022661:RNA, Untranslated; D013947:Thymosin; D000099201:Thymosin beta(4)