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

P Ji, S Diederichs, W Wang, S Böing, R Metzger… - Oncogene, 2003 - nature.com
P Ji, S Diederichs, W Wang, S Böing, R Metzger, PM Schneider, N Tidow, B Brandt
Oncogene, 2003nature.com
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 …
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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