Low expression of KLRB1 predicts poor survival outcomes and is associated with immune infiltration in breast cancer.

Abstract

KLRB1 is downregulated in various cancer types. Nevertheless, the specific involvement of KLRB1 in the context of breast cancer (BRCA) has not been fully elucidated. This research aimed to explore its clinical value in BRCA. A dataset comprising 1,109 BRCA samples and 113 healthy samples was retrieved from The Cancer Genome Atlas (TCGA) database to establish the association between KLRB1 expression and pan-cancer. Subsequently, an analysis was executed to explore the link between KLRB1 and BRCA. T-tests and Chi-squared tests were conducted to assess the expression of KLRB1 and its clinical implications in BRCA. The prognosis-predictive value of KLRB1 in BRCA was assessed using the Kaplan-Meier method and Cox regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses screened biological pathways to analyze the association between the immune infiltration level and KLRB1 expression in BRCA. Lastly, the conclusion was validated through quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Cell Counting Kit-8 (CCK8) assays. KLRB1 exhibited low expression in patients with BRCA. Furthermore, KLRB1 demonstrated strong diagnostic potential, as indicated by an area under curve (AUC) of 0.712. Kaplan-Meier survival and Cox regression analyses indicated that attenuated expression of KLRB1 was independently linked to unfavorable clinical outcomes. GO and KEGG enrichment analyses were performed on the top 10 genes that exhibited positive and negative correlations with KLRB1. Analysis of genes positively correlated with KLRB1 revealed associations with signaling receptor activator activity, lymphocyte proliferation, mononuclear cell proliferation, leukocyte proliferation, receptor-ligand activity, immunoglobulin binding, and hematopoietic cell lineage signaling pathway. KLRB1 expression exhibited significant correlations with all immune cells. Furthermore, qPCR and IHC outcomes demonstrated that KLRB1 was significantly downregulated in BRCA tissues. CCK8 findings showed a decrease in the proliferation of BRCA MCF7 cells upon knockout of KLRB1. This research investigated the mechanism and potential therapeutic target of the KLRB1 gene in BRCA. By analyzing the expression and function of the KLRB1 gene, the study aims to find its significant role in the onset and progression of BRCA. This research endeavors to offer novel strategies and approaches for treating BRCA.