Integrated analysis of pivotal biomarker, immune cell infiltration, and therapeutic drugs for LSM1-mutated in breast cancer.

Abstract

e13011 Background: The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Methods: In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of LSM1 in patients with breast cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of LSM1 proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichmente. Finally, we explored the mechanisms underlying LSM1 involvement in BRCA by using gene set enrichment analysis. Results: We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in BRCA patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. Conclusions: In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer.