Abstract
Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members’ gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.
Highlights
The World Health Organization (WHO) has provided statistical reports showing that cancer is one of the leading causes of premature death, and patient numbers are increasing due to an aging population [1]
We revealed mRNA expression from the LAGE gene family consisting of LAGE-1, LAGE2A, LAGE2B, and LAGE-3 in 20 cancer types (Figure 1)
The L-antigen family member 3 (LAGE3) gene family was overexpressed in breast cancer tissues compared to normal samples in 18 analyses (Figure 1A)
Summary
The World Health Organization (WHO) has provided statistical reports showing that cancer is one of the leading causes of premature death, and patient numbers are increasing due to an aging population [1]. Many alterations in essential enzyme activities in cancers were reported that disrupt cellular metabolic pathways [19,20] It is still unclear whether the immune and inflammation-related pathway were correlated with the LAGE family in BRCA. Due to their expeditiousness and robustness in screening potential targets in diseases, high-throughput technologies are playing critical roles in the biomedical fields. Since altered gene expressions have long been proposed to play a part in cancer development as oncogenes or tumor suppressors, there is a need to understand the different perceptions of LAGE family members between various subtypes of BRCA. The LAGE family’s functions in BRCA tumorigenesis in terms of the immune response are systematically discussed for the first time
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