Identification
of Metastasis-associated Genes in Early Stage Non-small Cell Lung Cancer by
Subtractive Hybridization
WANG Wen-Bing1,2*, BÖING
Sebastian1, ZHOU Xiao-Qin1, JI Ping1, DONG Yin2,
YAO Qin2, and MÜLLER-TIDOW Carsten1
( 1Department of Medicine, Hematology and Oncology,
University of Münster, Münster 48129, Germany; 2Institute
of life sciences, University of Jiangsu, Zhenjiang 212013, China )
Abstract Non-small
cell lung cancer (NSCLC) is a leading cause of death and asubstantial fraction
of patients with surgically resected disease ultimately dies due to distant
metastasis.To identify gene expression differences in early stage
adenocarcinoma that either did or did not metastasize within a 5-year period,
we employed a subtractive hybridization strategy of pooled RNA from primary
adenocarcinomas (stage I) of the lung. Individual clones (n=225) of the
subtracted cDNA library were sequenced. Further analyses of mRNA expression
levels in a cohort of 70 NSCLC patients (stage I to IIIA) showed that the
metastasis association of the identified genes was stage and histology
specific. Cox regression analyses identified two genes (EIF4A1, MALA1)
to be independent prognostic parameters for patients’ survival in stage I and
II disease.These findings could help to identify early-stage NSCLC patients at
high risk for the development of distant metastasis.
Key words metastasis; non-small cell lung cancer;
subtractive hybridization; gene; expression
*Corresponding author: Tel,
86-511-8791702; Fax, 86-511-8791923; e-mail, [email protected]