Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer.

Abstract

Simple SummaryThe roles of “like-Smith” (LSM) proteins in breast cancer development and their clinical relevance remain unclear. In this study, multiple analyses based on 3593 patients with breast cancer and their mRNA expression values were utilized to investigate the clinical relevance of LSM family genes, including cancer aggressiveness, immune cell infiltration, prognostic outcomes, and related signaling pathways. We revealed that LSM4 had higher expression levels in breast tumor and breast cancer sub-types than in normal samples, and was associated with poor survival outcomes. Interestingly, infiltration levels of most immune cell types, including cluster of differentiation for positive CD4+ T cells, CD8+ T cells, T-cell follicular helpers, and myeloid-derived suppressor cells were positively correlated with LSM4 expression in several subclasses of breast cancer (basal, human epidermal growth factor receptor 2 (HER2), luminal A, and luminal B).In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The “Like-Smith” (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan–Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21–1.51, p for trend = 3.4 × 10−7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as “Cell cycle role of APC in cell cycle regulation” and “Immune response IL-15 signaling via MAPK and PI3K cascade” in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.