Dataset Information

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.

ABSTRACT:

Background

CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials.

Patients and methods

Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration.

Results

Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman's R=?-0.50, P?ConclusionsTaken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.

SUBMITTER: Buisseret L

PROVIDER: S-EPMC5913595 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.

Buisseret L L Pommey S S Allard B B Garaud S S Bergeron M M Cousineau I I Ameye L L Bareche Y Y Paesmans M M Crown J P A JPA Di Leo A A Loi S S Piccart-Gebhart M M Willard-Gallo K K Sotiriou C C Stagg J J

Annals of oncology : official journal of the European Society for Medical Oncology 20180401 4

<h4>Background</h4>CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials.<h4>Patients and methods</h4>Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial w ...[more]

PMID: 29145561

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Project description:PurposeThis study aimed to investigate the diagnostic and prognostic values of neuropilin-1 (NRP-1) in triple-negative breast cancer (TNBC) and analyze its immune function in the tumor microenvironment.MethodsBased on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, Genotype Tissue Expression, Immune Cell Abundance Identifier (ImmuCellAI), Reactome, and Genomics of Drug Sensitivity in Cancer databases, the cancer tissues from 50 patients with TNBC and corresponding adjacent noncancerous tissues from 10 patients (tissue microarrays were purchased from Shanghai Xinchao Biotechnology Co., Ltd.) were collected for validation. Bioinformatics combined with immunohistochemistry was used to analyze the relationship among NRP-1 expression, prognosis, tumor immune cell infiltration, immune genes, and drug resistance so as to investigate the role of NRP-1 in the development of TNBC.ResultsA significant difference in NRP-1 gene expression was found between the cancerous and noncancerous tissues (p-value < 0.05); NRP-1 expression was high in carcinoma. No significant correlation was found between NRP-1 protein expression levels and each stage in the TCGA database. Prognostic expression survival analysis showed that the survival probability of patients with high NRP-1 expression was significantly lower than that of patients with low NRP-1 expression (p-value < 0.05), suggesting that the gene might be a pro-oncogene. The data from 50 clinical samples also confirmed that the NRP-1 expression was significantly higher in triple-negative breast cancer (TNBC) tissues than in adjacent noncancerous tissues. The NRP-1 expression significantly correlated with the tumor diameter and pathological grade (p-value < 0.05), but not with age, stage, and ki67 (p-value > 0.05). The Kaplan-Meier survival curves suggested that the median overall survival was significantly shorter in patients with high NRP-1 expression than in those with low NRP-1 expression (13.6 months vs 15.2 months, p-value < 0.05). The 300 genes most significantly positively associated with this gene were selected for Gene Ontology (including Biological Process, Molecular Function, and Cellular Component groups) and Kyoto Encyclopedia of Genes and Genomics enrichment analysis. The findings showed that NRP-1 was involved in immune regulation in TNBC. In addition, the NRP-1 expression in TNBC positively correlated with a variety of immune cells and checkpoints.ConclusionNRP-1 can be used as a potential biomarker and therapeutic target in TNBC.

Dataset Information

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.

Background

Patients and methods

Results

Publications

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.

Similar Datasets

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