The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis

Abstract

Lung cancer has been a leading cause of cancer-related death for decades and therapeutic strategies for non-driver mutation lung cancer are still lacking. A novel approach for this type of lung cancer is an emergent requirement. Here we find that loss of LSAMP (Limbic System Associated Membrane Protein), compared to other IgLON family of proteins NTM (Neurotrimin) and OPCML (OPioid-binding Cell adhesion MoLecule), exhibits the strongest prognostic and therapeutic significance in predicting lung adenocarcinoma (LUAD) progression. Lower expression of <i>LSAMP</i> and <i>NTM</i>, but not <i>OPCML</i>, were found in tumor parts compared with normal parts in six LUAD patients, and this was validated by public datasets, Oncomine^® and TCGA. The lower expression of <i>LSAMP</i>, but not <i>NTM</i>, was correlated to shorter overall survival. Two epigenetic regulations, including hypermethylation and miR-143-3p upregulation but not copy number variation, were associated with downregulation of <i>LSAMP</i> in LUAD patients. Pathway network analysis showed that NEGR1 (Neuronal Growth Regulator 1) was involved in the regulatory loop of LSAMP. The biologic functions by <i>LSMAP</i> knockdown in lung cancer cells revealed <i>LSMAP</i> was linked to cancer cell migration via epithelial-mesenchymal transition (EMT) but not proliferation nor stemness of LUAD. Our result showed for the first time that <i>LSAMP</i> acts as a potential tumor suppressor in regulating lung cancer. A further deep investigation into the role of <i>LSAMP</i> in lung cancer tumorigenesis would provide therapeutic hope for such affected patients.