CD52 Is a Prognostic Biomarker and Associated With Tumor Microenvironment in Breast Cancer

Wang, Jianxin; Zhang, Guangchen; Sui, Yang; Zhong, Yang; Chu, Yinzhu; Tang, Hailing; Guo, Binbin; Zhang, Cong; Wu, Changjun

doi:10.3389/fgene.2020.578002

Cited by 35 publications

(27 citation statements)

References 26 publications

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“…Further analysis demonstrated that CCL19, CD3E, and ITK were not strongly associated with OS in our sample. However, previous research demonstrated that CD52 can play a significant prognostic role in BRCA patients (23). CD2 is an essential component in the immunological synapse, the actin cytoskeleton, and agonistic cell signaling, and it is expressed on the surface of T, NK, and dendritic cells (24).…”

Section: Discussionmentioning

confidence: 99%

CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment

et al. 2021

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Female breast cancer (BCa) is the most commonly occurring cancer worldwide. The tumor microenvironment (TME) plays an essential role in tumor invasion, angiogenesis, unlimited proliferation, and even immune escape, but we know little about the TME of BCa. In this study, we aimed to find a TME-related biomarker for BCa, especially for invasive breast carcinoma (BRCA), that could predict prognosis and immunotherapy efficacy. Based on RNA-seq transcriptome data and the clinical characteristics of 1222 samples (113 normal and 1109 tumor samples) from The Cancer Genome Atlas (TCGA) database, we used the ESTIMATE algorithm to calculate the ImmuneScore and StromalScore and then identified differentially expressed genes (DEGs) between the high and low ImmuneScore groups and the high and low StromalScore groups. Thereafter, a protein–protein interaction (PPI) network analysis and univariate Cox regression analyses of overall survival were used to identify potential key genes. Five candidate genes were identified, comprising CD2, CCL19, CD52, CD3E, and ITK. Thereafter, we focused on CD2, analyzing CD2 expression and its association with survival. CD2 expression was associated with tumor size (T stage) to some extent, but not with overall TNM stage, lymph node status (N stage), or distant metastasis (M stage). High CD2 expression was associated with longer survival. METABRIC data were used to validate the survival result (n = 276). Gene set enrichment analysis (GSEA) showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly associated with high CD2 expression were mainly immune-related pathways. Furthermore, CD2 expression was correlated with 16 types of tumor-infiltrating immune cells (TICs). Hence, CD2 might be a novel biomarker in terms of molecular typing, and it may serve as a complementary approach to TNM staging to improve clinical outcome prediction for BCa patients.

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Section: Discussionmentioning

confidence: 99%

CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment

et al. 2021

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“…It is the target of the monoclonal antibody therapy alemtuzumab in several diseases including chronic lymphocytic leukemia, cutaneous T‐cell lymphoma (CTCL), and multiple sclerosis (MS) 39 . In breast cancer stromal tissue, CD52 has been linked to an expression signature of poor outcome, 40,41 our results give further evidence of the potential of its overexpression as marker of immune cell invasion in breast tumors.…”

Section: Discussionmentioning

confidence: 58%

Immunophenotype‐associated gene signature in ductal breast tumors varies by receptor subtype, but the expression of individual signature genes remains consistent

Behring

Elkholy

et al. 2021

Cancer Medicine

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Background In silico deconvolution of invasive immune cell infiltration in bulk breast tumors helps characterize immunophenotype, expands treatment options, and influences survival endpoints. In this study, we identify the differential expression (DE) of the LM22 signature to classify immune‐rich and ‐poor breast tumors and evaluate immune infiltration by receptor subtype and lymph node metastasis. Methods Using publicly available data, we applied the CIBERSORT algorithm to estimate immune cells infiltrating the tumor into immune‐rich and immune‐poor groups. We then tested the association of receptor subtype and nodal status with immune‐rich/poor phenotype. We used DE to test individual signature genes and over‐representation analysis for related pathways. Results CCL19 and CXCL9 expression differed between rich/poor signature groups regardless of subtype. Overexpression of CHI3L2 and FES was observed in triple negative breast cancers (TNBCs) relative to other subtypes in immune‐rich tumors. Non‐signature genes, LYZ, C1QB, CORO1A, EVI2B, GBP1, PSMB9, and CD52 were consistently overexpressed in immune‐rich tumors, and SCUBE2 and GRIA2 were associated with immune‐poor tumors. Immune‐rich tumors had significant upregulation of genes/pathways while none were identified in immune‐poor tumors. Conclusions Overall, the proportion of immune‐rich/poor tumors differed by subtype; however, a subset of 10 LM22 genes that marked immune‐rich status remained the same across subtype. Non‐LM22 genes differentially expressed between the phenotypes suggest that the biologic processes responsible for immune‐poor phenotype are not yet well characterized.

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“…With the better understanding of the association between lncRNAs and the immune system (23,24), more and more evidence indicates that lncRNAs can not only act as diagnostic biomarkers, but also prognostic signatures for cancer patients. Several studies have focused on using coding genes and noncoding RNAs to construct models to assess the prognostic and diagnostic values for BRCA (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Using immune-related lncRNAs to construct novel biomarkers and investigate the immune landscape of breast cancer

Qin¹,

Ma²,

Wang³

et al. 2021

Transl Cancer Res TCR

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Background: The role of immune-related long noncoding RNAs (irlncRNAs) in breast cancer (BRCA) is still unclear. Recently, studies have performed analyses based on the expression of irlncRNAs, however, in the present study, we used a novel method that did not require the specific expression levels of lncRNAs of BRCA patients. Methods:We downloaded transcriptome and clinical data of BRCA patients from The Cancer Genome Atlas (TCGA), obtained immune genes from the Immport database, and extracted immune genes and lncRNAs for correlation analysis. Then, the differential expression of irlncRNA pairs (IRLPs) was determined and the prognostic signature was established by the IRLPs. The immune cell abundance of the TCGA-BRCA cohort was downloaded from the Tumor IMmune Estimation Resource (TIMER) database, and the relationship between the risk score of the IRLP signature and immune cell abundance was analyzed. Finally, we explored the relationship between risk scores and drug sensitivity based on the R package pRRophetic.Results: Univariate cox regression results showed that 33 IRLPs had significant effects on the overall survival (OS) of BRCA patients. Then 22 IRLPs were obtained via lasso regression for further analysis.Multivariate regression analysis obtained 12 IRLPs to establish the IRLP prognostic signature. The model showed that this IRLP signature could act as a prognostic biomarker for BRCA patients. Kaplan-Meier (KM) survival analysis indicated that low-risk patients of IRLP's signature had a better OS (P<0.001). Advanced status BRCA patients may have higher risk scores, and univariate and multivariate cox regression analyses showed that risk scores were independent prognostic factors of clinical features (P<0.001). The results of the relationship between risk scores and immune infiltration showed that M1 macrophages were higher in the low-risk group (P=0.00015), while M2 macrophages were higher in the high-risk group (P=0.0015). The high-risk group had a greater sensitivity to chemotherapeutic agents such as cisplatin, docetaxel, doxorubicin, and gemcitabine. Conclusions:In present study, we used a novel method that did not require the specific expression levels of lncRNAs of BRCA patients, which can be used as a novel model for predicting the prognosis of BRCA patients.

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CD52 Is a Prognostic Biomarker and Associated With Tumor Microenvironment in Breast Cancer

Cited by 35 publications

References 26 publications

CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment

CD2 Is a Novel Immune-Related Prognostic Biomarker of Invasive Breast Carcinoma That Modulates the Tumor Microenvironment

Immunophenotype‐associated gene signature in ductal breast tumors varies by receptor subtype, but the expression of individual signature genes remains consistent

Using immune-related lncRNAs to construct novel biomarkers and investigate the immune landscape of breast cancer

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