Dataset Information

Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype.

ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer, which is characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative. TNBC is the most difficult breast cancer subgroup to treat, due to its unresponsiveness to current clinical targeted therapies, high rate of recurrence, and poor prognosis. Thus, there is an urgent medical need to identify therapeutic targets and develop more effective stratified medicine for the treatment of TNBC. Here we review the potential therapeutic targets for TNBC based on its intrinsic subtype. We also review the aberrant activated signals found in different subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch, Wnt/?-catenin, Hedge-hog, and TGF-? signaling pathways, which play essential roles in multiple development stages of TNBC. The careful analysis of these signaling pathways and therapeutic targets would have significant impact on the drug development and clinical trials, leading to effective therapies for this deadly disease.

SUBMITTER: Shao F

PROVIDER: S-EPMC5641215 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype.

Shao Fangyuan F Sun Heng H Deng Chu-Xia CX

Oncotarget 20170816 42

Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer, which is characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative. TNBC is the most difficult breast cancer subgroup to treat, due to its unresponsiveness to current clinical targeted therapies, high rate of recurrence, and poor prognosis. Thus, there is an urgent medical need to identify therapeutic targets and develop ...[more]

PMID: 29069872

Similar Datasets

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

Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype.

Publications

Potential therapeutic targets of triple-negative breast cancer based on its intrinsic subtype.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets