The prognostic significance of KLRB1 and its further association with immune cells in breast cancer

Abstract

Background Killer cell lectin-like receptor B1 (KLRB1) is an important member of the natural killer cell gene family. This study explored the potential value of KLRB1 as a breast cancer (BC) biomarker and its close association with the tumor immune microenvironment during the development of BC. Methods We examined the differential expression of KLRB1 in pan-cancer. Clinical and RNA-Seq data from BC samples were evaluated in The Cancer Genome Atlas (TCGA) and validated in Gene Expression Omnibus (GEO) datasets and by immunohistochemistry (IHC) staining. The relationship between KLRB1 and clinical parameters was explored through Chi-square tests. The diagnostic value of KLRB1 was evaluated using a receiver operating characteristic (ROC) curve. Survival analysis was tested by Kaplan-Meier curves to demonstrate the relationship between KLRB1 and survival. Univariable and multivariate cox regression analyses were carried out as well. The analysis of immune infiltration level and gene set enrichment analysis (GSEA) were conducted to examine KLRB1’s mechanism during the progression of BC. We used the Tumor Immune Estimation Resource (TIMER), the Cancer Single-cell Expression Map (CancerSCEM) database, the Tumor Immune Single-cell Hub (TISCH) database, and the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) method to explore KLRB1’s association with immune infiltration level and different quantitative distribution of immune cells. The relevant signaling pathways in BC associated with KLRB1 were identified using GSEA. Results The expression of KLRB1 was downregulated across the majority of cancers including BC. The lower KLRB1 expression group exhibited shorter relapse free survival (RFS) and overall survival (OS). IHC staining showed that KLRB1 staining was weaker in breast tumor tissues than in paratumors. Additionally, GSEA identified several pathway items distinctly enriched in BC. KLRB1 expression level was also positively related to the infiltrating number of immune cells in BC. Moreover, the CancerSCEM and TISCH databases as well as the CIBERSORT method demonstrated the close relationship between KLRB1 and immune cells, particularly macrophages. Conclusion Low KLRB1 expression was considered an independent prognostic biomarker and played an important role in the tumor immune microenvironment of BC patients.

KLRB1 expression is associated with lung adenocarcinoma prognosis and immune infiltration and regulates lung adenocarcinoma cell proliferation and metastasis through the MAPK/ERK pathway

“…KLRB1 is located on human chromosome 12 and encodes CD161 that is expressed on the surface of most NK cells and T lymphocytes ( 4 ). Studies have shown that inhibition of KLRB1 expression in breast invasive carcinoma is associated with impaired tumor immune function, leading to tumor progression and poor prognosis ( 28 , 29 ). Downregulation of KLRB1 expression is strongly associated with poor survival outcomes in EC and can influence tumor progression by affecting immune cell infiltration subpopulations in the TME ( 30 ).…”

Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients

“…Moreover, SPARC secreted by CAFs promotes tumor growth by inhibiting adhesion of triple-negative BC cells whilst stimulating invasion and metastasis [19]. Recently, KLRB1 has become an increasing focus in tumor research as it has been associated with tumor progression [11][12][13][14][15]20]. Xu and Huang et al found that KLRB1 is a tumor suppressor gene involved in the BC progression.…”

“…Studies have shown that KLRB1 gene inactivation enhances T-cell-mediated killing of glioma cells in vitro and the anti-tumor function of KLRB1 in vivo [ 13 ], whereas decreased KLRB1 expression has been associated with poor prognosis in BC patients [ 11 ]. Xu and Huang et al found that KLRB1 is in the down-regulation trend in BC and a negative correlation between overexpression of KLRB1 and poor prognosis (such as overall survival (OS) and recurrence free survival (RFS)) of BC patients through survival analysis [ 14 , 15 ]. However, not much is known about the relationship between KLRB1 expression and BC subtypes (such as the BRCA) progression.…”

A comprehensive analysis of the KLRB1 expression and its clinical implication in testicular germ cell tumors: A review

“…[ 15 ] Currently, KLRB1 has shown potential biomarker value and immunomodulatory effects in breast cancer, esophageal squamous cell carcinoma, and glioma. [ 16 – 18 ] In addition, KLRB1 enhances the progression and evolution of gliomas through its unique effect on T-cell dysfunction. [ 18 ] However, the correlation between KLRB1 expression in TGCT and its biological function is unclear.…”