Characterization of SEZ6L2 cell-surface protein as a novel prognostic marker for lung cancer.
To identify molecules that might serve as biomarkers or targets for development of novel molecular therapies, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using cDNA microarrays coupled with purification of tumor cells by laser microdissection. A gene encoding seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) protein, was chosen as a candidate for such molecule. Semi-quantitative RT-PCR and western-blot analyses documented increased expression of SEZ6L2 in the majority of primary lung cancers and lung-cancer cell lines examined. SEZ6L2 protein was proven to be present on the surface of lung-cancer cells by flow cytometrical analysis using anti-SEZ6L2 antibody. Immunohistochemical staining for tumor tissue microarray consisting of 440 archived lung-cancer specimens detected positive SEZ6L2 staining in 327 (78%) of 420 non-small cell lung cancers (NSCLCs) and 13 (65%) of 20 small-cell lung cancers (SCLCs) examined. Moreover, NSCLC patients whose tumors revealed a higher level of SEZ6L2 expression suffered shorter tumor-specific survival compared to those with no SEZ6L2 expression. These results indicate that SEZ6L2 should be a useful prognostic marker of lung cancers.
Ishikawa
Nobuhisa
N
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Daigo
Yataro
Y
Takano
Atsushi
A
Taniwaki
Masaya
M
Kato
Tatsuya
T
Tanaka
Sonosuke
S
Yasui
Wataru
W
Takeshima
Yukio
Y
Inai
Kouki
K
Nishimura
Hitoshi
H
Tsuchiya
Eiju
E
Kohno
Nobuoki
N
Nakamura
Yusuke
Y
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C513545:SEZ6L2 protein, human