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 LSAMP and NTM, but not OPCML, 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 LSAMP, but not NTM, 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 LSAMP 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 LSMAP knockdown in
lung cancer cells revealed LSMAP 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 LSAMP acts as a potential
tumor suppressor in regulating
lung cancer. A further deep investigation into the role of LSAMP in
lung cancer tumorigenesis would provide therapeutic hope for such affected patients.