Cancer testis antigen, nol4, is an immunogenic antigen specifically expressed in small‐cell lung cancer

Abstract

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small‐cell lung cancer cell line NCI‐H889 cDNA libraries was performed using serum obtained from a small‐cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones com-prised of 74 different genes, designated KP‐SCLC‐1 through KP‐SCLC‐74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP‐ SCLC‐29 (NOL4), KP‐SCLC‐59 (CCDC83), and KP‐SCLC‐69 (KIF20B), were CT antigens. RT‐PCR and western blot analysis showed that NOL4 was frequently present in small‐cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small‐cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small‐cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.