TY - JOUR
T1 - MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer
AU - Ji, Ping
AU - Diederichs, Sven
AU - Wang, Wenbing
AU - Böing, Sebastian
AU - Metzger, Ralf
AU - Schneider, Paul M.
AU - Tidow, Nicola
AU - Brandt, Burkhard
AU - Buerger, Horst
AU - Bulk, Etmar
AU - Thomas, Michael
AU - Berdel, Wolfgang E.
AU - Serve, Hubert
AU - Müller-Tidow, Carsten
N1 - Funding Information:
*Correspondence to: H Serve and C Müller-Tidow, Department of Medicine, Hematology/Oncology, University of Münster Domagkstr. 3, 48129 Münster, Germany; E-mail: [email protected] This work is supported by a grant from the Wilhelm Sander-Stiftung (2001.086.1) 5Contributed equally Received 26 April 2002; revised 16 June 2003; accepted 30 June 2003
PY - 2003/9/11
Y1 - 2003/9/11
N2 - 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.
AB - 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.
KW - MALAT-1
KW - Metastasis
KW - Non-small cell lung cancer
KW - Prognostic parameter
KW - Subtractive hybridization
KW - Thymosin β4
UR - http://www.scopus.com/inward/record.url?scp=0344429906&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344429906&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1206928
DO - 10.1038/sj.onc.1206928
M3 - Article
C2 - 12970751
AN - SCOPUS:0344429906
SN - 0950-9232
VL - 22
SP - 8031
EP - 8041
JO - Oncogene
JF - Oncogene
IS - 39
ER -