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. (Cancer Sci 2006; 97: 737–745)

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