A comprehensive function analysis of LMO2 in different breast cancer subtypes

Abstract

Breast cancer is the most common invasive cancer in women worldwide, and can be subdivided into Luminal A, Luminal B, Her2, and Basal subtype (the PAM50 subtyping system). The lmo2 gene was traditionally recognized as a proto-oncogene in hematopoietic system but its functions in breast cancers remained largely unclear. Based on the Cancer Genome Atlas (TCGA) breast cancer dataset, herein we found that the significantly LMO2-correlated genes in normal or malignant samples were enriched in rather divergent cellular pathways, suggesting the function complexity of LMO2 in breast tissues. Moreover, high LMO2 expression level was found to predict a shorter patient survival in Luminal A type whereas a better outcome in Her2 type. Correspondingly, LMO2 also revealed function diversities in different PAM50 subtypes. In Luminal A type, the LMO2 related genes were primarily enriched in cancer-promoting pathways, including VEGF production, stemness, PPAR signal pathways, MAPK cascade and cell cycle regulation. In Her2 type however, the LMO2 related genes lacked the enrichment on most of the generally cancer-related pathways and were particularly enriched in negative regulation of ErbB pathway as well as MAPK cascade, suggesting a potentially anti-oncogenic role of LMO2 on this subtype. Taken together, this study drew a comprehensive overview of divergent functions of LMO2 on breast cancers, provided additional evidence for the function complexity of LMO2 in solid tumors and suggested the potential usage of LMO2 as a PAM50 subtype dependent biomarker for breast cancer clinic in the precision medicine era.