CLEC10A can serve as a potential therapeutic target and its level correlates with immune infiltration in breast cancer

Abstract

Breast cancer (BC) is one of the most common malignant cancers in females worldwide and greatly threatens women's health. The C-type lectin domain family 10 member A (CLEC10A) is a member of the C-type lectin receptor family that has been previously reported to promote the antitumor activity of immune cells. In the present study, the potential prognostic value of CLEC10A expression in BC was assessed using data from The Cancer Genome Atlas online database. Differences in the mRNA expression levels of CLEC10A between BC and normal tissues were then analyzed using the Tumor Immune Estimation Resource (TIMER) platform and the University of Alabama at Birmingham Cancer data analysis portal. Reverse transcription-quantitative PCR was performed to validate the results of this analysis. The Kaplan-Meier plotter database was used to evaluate the association between the mRNA expression levels of CLEC10A and clinical prognosis of BC. Based on the association between the mRNA expression levels of CLEC10A and the tumor immune microenvironment, the TIMER platform and the Tumor and Immune System Interaction Database website were utilized to assess the correlation between CLEC10A expression and the degree of tumor immune cell infiltration. The present study revealed that CLEC10A expression was significantly lower in BC tissues compared with that in normal tissues, which was in turn associated with poorer clinical outcomes. This suggested that lower CLEC10A expression levels were associated with unfavorable prognosis in BC. In addition, the expression level of CLEC10A was found to be positively associated with the level of different tumor-infiltrating immune cells in BC, including CD8 T cells, B cells, macrophages and NK cells which, was in turn closely correlated with some gene markers such as CD19, CD8A, KIR2DS4 and PTGS2. These results suggest that the relationship between lower CLEC10A expression level and poor prognosis in BC may be due to the role of CLEC10A in the tumor immune microenvironment. In conclusion, CLEC10A may be a potential biomarker that can be used to efficiently predict prognosis in patients with BC.

Keywords: C-type lectin domain family 10 member A; biomarkers; breast cancer; immune cell; overall survival; prognosis.

Figure 1.

Expression levels of the CLEC10A gene in different cancers and their association with individual clinical parameters of BC. (A) CLEC10A gene expression levels in different cancer tissues compared with normal tissues in the Tumor IMmune Estimation Resource database. (B) Difference in the CLEC10A gene expression levels between primary BCs and unmatched normal samples from the TCGA-BRCA data sets using Mann-Whitney U test. (C) Difference in the CLEC10A gene expression levels between primary BCs and matched normal samples from the TCGA-BRCA data sets using Wilcoxon signed-rank test. (D) Reverse transcription-quantitative PCR analysis of the mRNA expression levels of CLEC10A in normal breast epithelial and breast cancer cell lines. Mann Whitney U test of the association between CLEC10A gene expression from the TCGA-BRCA datasets and (E) clinical T, (F) clinical N and (G) pathological stages, (H) ER and (I) HER2 statuses. *P<0.05, **P<0.01, ***P<0.001. ns, not significant; CLEC10A, C-type lectin domain family 10 member A; BC, breast cancer; COAD, colon adenocarcinoma; ACC, adrenocortical carcinoma; READ, rectum adenocarcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical and endocervical cancer; CHOL, cholangiocarcinoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; UVM, uveal melanoma; SKCM, skin cutaneous melanoma; LUSC, lung squamous cell carcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; STAD, stomach adenocarcinoma; THCA, thyroid carcinoma; UCEC, uterine corpus; DLBCL, diffuse large B cell lymphoma; LAML, acute myeloid leukemia; LGG, low-grade glioma; MESO, mesothelioma; OV, ovarian cancer; PAAD, pancreatic adenocarcinoma; SARC, sarcoma; TGCT, tenosynovial giant cell tumor; THYM, thymoma; UCS, uterine carcinosarcoma; FPKM, fragments per kilobase of exon per million mapped fragments; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2.

Figure 2.

Predictive value of the CLEC10A gene expression levels for the diagnosis and prognosis in patients with BC. (A) Receiver operating characteristic curve analysis evaluating the performance of CLEC10A gene expression for BC diagnosis. (B) Kaplan-Meier analysis comparing the overall survival of patients in the high and low CLEC10A gene expression groups. (C) Kaplan-Meier analysis comparing the disease-specific survival of patients in the high and low CLEC10A gene expression groups. (D) Kaplan-Meier analysis comparing the progression-free interval of patients in the high and low CLEC10A gene expression groups. BC, breast cancer; CLEC10A, C-type lectin domain family 10 member A; HR, hazard ratio; FPR, false-positive rate; TPR, true-positive rate.

Figure 3.

Forest plot of the prognostic value of C-type lectin domain family 10 member A gene expression in 30 The Cancer Genome Atlas tumors. (A) Overall survival HR. (B) Progression-free survival HR. HR, hazard ratio.

Figure 4.

Association analysis of CLEC10A gene expression and immune infiltration using the Tumor And Immune System Interaction Database by Spearman's correlation analysis. (A) Relationships between the gene expression of CLEC10A and 28 types of tumor-infiltrating lymphocytes among a panel of heterogeneous human cancers. Correlation of CLEC10A gene expression with the degree of infiltration by (B) B, (C) CD8+ T, (D) macrophages, (E) dendritic, (F) NK, (G) Tcm, (H) Th1, (I) Th17 cells and (J) neutrophils. CLEC10A, C-type lectin domain family 10 member A; Tcm, T central memory; NK, natural killer; DC, dendritic cells; FPKM, fragments per kilobase per million.

Figure 5.

Comparison of Kaplan-Meier survival curves of the expression of CLEC10A in patients with breast cancer based on the immune cell subgroups. (A) CD4+ T cells. (B) Macrophages. (C) Neutrophils. (D) NK cells. (E) Th2 cells. (F) Mesenchymal stem cells. CLEC10A, C-type lectin domain family 10 member A; NK, natural killer; HR, hazard ratio.