Dataset Information

Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets.

ABSTRACT: Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer. High invasiveness and heterogeneity, as well as a lack of drug targets, are the main factors leading to poor prognosis. Brain metastasis (BM) is a serious event threatening the life of breast cancer patients, especially those with TNBC. Compared with that for hormone receptor-positive and HER2-positive breast cancers, TNBC-derived BM (TNBCBM) occurs earlier and more frequently, and has a worse prognosis. There is no standard treatment for BM to date, and one is urgently required. In this review, we discuss the current knowledge regarding the developmental patterns of TNBCBM, focusing on the key events in BM formation. Specifically, we consider (i) the nature and function of TNBC cells; (ii) how TNBC cells cross the blood-brain barrier and form a fenestrated, more permeable blood-tumor barrier; (iii) the biological characteristics of TNBCBM; and (iv) the infiltration and colonization of the central nervous system (CNS) by TNBC cells, including the establishment of premetastatic niches, immunosurveillance escape, and metabolic adaptations. We also discuss putative therapeutic targets and precision therapy with the greatest potential to treat TNBCBM, and summarize the relevant completed and ongoing clinical trials. These findings may provide new insights into the prevention and treatment of BM in TNBC patients.

SUBMITTER: Lv Y

PROVIDER: S-EPMC7837592 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets.

Lv Yan Y Ma Xiao X Du Yuxin Y Feng Jifeng J

OncoTargets and therapy 20210122

Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer. High invasiveness and heterogeneity, as well as a lack of drug targets, are the main factors leading to poor prognosis. Brain metastasis (BM) is a serious event threatening the life of breast cancer patients, especially those with TNBC. Compared with that for hormone receptor-positive and HER2-positive breast cancers, TNBC-derived BM (TNBCBM) occurs earlier and more frequently, and has a worse prognosis. There i ...[more]

PMID: 33519208

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Project description:PurposeTriple-negative breast cancer (TNBC) is an aggressive tumor with poor prognosis, it has higher recurrence and metastatic rates than other breast cancer subtypes. This study aims to investigate biomarkers and potential targets for TNBC related to ferroptosis through data mining and bioinformatics analysis. The findings may provide new insights for treating TNBC.MethodsThe TNBC patients' data from the Cancer Genome Atlas (TCGA) database were extracted for differential expression and prognosis analysis. Consensus genes obtained by intersecting differential expressed and ferroptosis-related genes was used to establish the prognostic model by the univariate and multivariate Cox analyses. Besides, TNBC data from the Gene Expression Omnibus (GEO) database was used to confirm the reliability of the prognosis model. Moreover, clinical information was analyzed by multifactorial independent analysis to identify independent prognostic factors. The expression of genes constituting the prognostic model was further validated using the Human Protein Atlas (HPA) database. Finally, the Comparative Toxicogenomic Data (CTD) database was used to explore possible treatment drugs for TNBC.ResultsWe obtained 13,245 differential expressed genes, and 177 consensus genes. 98 genes with prognostic implication were obtained by univariable Cox. Then, a prognostic model including 12 ferroptosis-related genes was constructed by multivariable Cox. The area under curve (AUC) value of the prognostic model for TNBC was 0.82. The GEO database validated that the model (AUC = 0.77) could predict the patient outcomes. The staining results of 10 out of 12 prognostic model genes in HPA database showed that their expression was consistent with our predictions. Clinical risk analysis indicated that risk score of patients could act as an independent prognostic factor. Finally, six drugs that may have interaction with 12 ferroptosis-related genes were obtained using the CTD database.ConclusionThe prognostic model composed of 12 ferroptosis-related genes could predict the prognosis of TNBC patients, and seven genes (ASNS, LAMP2, CAV1, DPP4, HELLS, TF, ZFP69B) could be potential new therapeutic targets for TNBC, and two drugs (1-methyl-3-isobutylxanthine, rosiglitazone) could act as potential therapeutic drugs for the treatment of TNBC.

Dataset Information

Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets.

Publications

Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets.

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