Lung cancer is the leading cause of cancer deaths worldwide. The prognosis of patients with lung cancer remains poor, because of its occult metastasis even at earlier stage of the disease and its resistance to conventional multimodal treatments. Therefore, this study aims to identify novel serum and tissue biomarkers for personalized therapy and/or therapeutic targets for lung cancers through screening and functional analyses of cancer-specific oncoproteins. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, and identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical staining of LASEP3 showed that LASEP3 expression was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP3 expression was associated with poor prognosis for NSCLC patients. (P = 0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs (49.4% for stage I-II, 67.4% for stage III-IV), while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover, reduction of LASEP3 expression by siRNAs suppressed lung cancer cell proliferation, probably through apoptosis as suggested by flow cytometric analysis and caspase-3 and 7 assays. Furthermore, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEP3 that relate to cell growth and invasion signals. LASEP3 is a possible diagnostic and prognostic biomarker and a therapeutic target for lung cancer.
Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Identification of LASEP3 as a serological and tissue biomarker and a therapeutic target for lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1875.