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

PeerJ

article

Ning Xu¹  Xiangyu Meng²  Hongyu Chu³  Zhaoying Yang²  Yan Jiao⁴  Youjun Li¹ 

[1] Department of Human Anatomy, Jilin University;Department of Breast Surgery, China-Japan Union Hospital of Jilin University;Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University;Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University

关键词: Killer cell lectin-like receptor B1 (KLRB1);    Breast cancer;    Prognosis;    Biomarker;    Tumor immune microenvironment;    Macrophages;   

DOI  :  10.7717/peerj.15654

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundKiller 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.MethodsWe 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.ResultsThe 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.ConclusionLow KLRB1 expression was considered an independent prognostic biomarker and played an important role in the tumor immune microenvironment of BC patients.

【 授权许可】

CC BY