Elevated expression of LRRC15 Shows Putative Tumor-promoting Characteristics in tumor microenvironment of breast cancer

Abstract

Background Leucine-rich repeat containing 15 (LRRC15), belongs to the LRR superfamily and has emerged as a marker of cancer-associated fibroblasts. It was found to be particularly upregulated in breast cancer (BCa). This study aimed to investigate the correlation between LRRC15 expression and immune microenviroment and visualize its prognostic landscape in BCa. Methods The mRNA expression level, prognostic value, correlation of immunity, gene-gene interaction network of LRRC15 in BCa were analyzed utilizing the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, and TIMER database. We next analyzed the biological functions of LRRC15 and pathways of its co-expressed genes, and its correlation with immune system responses via the Metascape and GeneMANIA database, respectively. We validated the expression of LRRC15 in BCa via western blot and IHC assays and analyzed its correlation with clinicopathological parameters. Results We explored LRRC15 expression in multiple types of cancer based on the Cancer Genome Atlas (TCGA) database, with the effect being particularly pronounced in BCa. Both mRNA and protein abundance of LRRC15 were significantly elevated in BCa as compared to its non-tumor counterparts. Overexpression of LRRC15 significantly associated with reduced overall survival. LRRC15 knockdown significantly inhibited cell proliferation and cell cycle in BCa cells. There were significant positive correlations between LRRC15 expression and tumor-infiltrating immune cells (TIICs), with a particularly strong effect on macrophage infiltration. Moreover, markers of TIICs exhibited different LRRC15-related immune infiltration patterns. GSEA analysis showed that upregulated expression of LRRC15 was related to ECM receptor interaction, focal adhesion, regulation of actin cytoskeleton, and TGF Beta signaling pathway. Conclusions These findings revealed that LRRC15 served as a novel prognostic biomarker and putative oncogene for BCa by promoting cell proliferation, giving a novel hint for therapeutics of BCa.