Abstract 3927: Genome-wide screening and validation of molecular targets and biomarkers for lung cancer

Abstract

Abstract The number of lung cancer patients who respond well to currently available standard therapies is still small, new molecular targeted therapies with companion diagnostics are eagerly needed. We have been developing new molecular therapies targeting oncoproteins with their cancer biomarkers as follows, i) To identify strongly expressed genes in 120 lung cancers by genome-wide gene expression profile analysis, ii) To verify the candidate genes for their scarce expression in 23 normal organs, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering about 400 lung cancers (non-small cell lung cancers (NSCLCs) and SCLCs), iv) To examine their importance in the growth and/or invasion of cancer cells by siRNA, small molecule inhibitor, cell permeable peptides targeting their function and/or antibody assays, and v) To analyze the oncogenic function of the target molecules. By this system, we identified 50 oncoproteins and selected a LSERT (lung cancer-specific receptor tyrosine kinase) as a candidate. Immunocytochemical and immunohistochemical analyses confirmed that LSERT protein was expressed in cytoplasm and cytoplasmic membrane of lung cancer cells, but it was hardly expressed in normal lung cells. Strong LSERT expression was associated with poorer prognosis for surgically-treated NSCLC patients, and it was an independent prognostic factor. Exogenous expression of LSERT increased the cell growth and invasion probably through its elevated kinase activity and subsequent phosphorylation of downstream proteins. Inhibition of LSERT expression by siRNAs or treatment with anti-LSERT antibody suppressed the growth of lung cancer cells. Our genome-wide screening might be a useful approach to identify target molecules for developing new therapeutics and diagnostics. LSERT could be a candidate cancer biomarker and therapeutic target for lung cancer. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Genome-wide screening and validation of molecular targets and biomarkers for lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3927.