scholarly journals A combined hypoxia and immune gene signature for predicting survival and risk stratification in triple-negative breast cancer

Aging ◽  
2021 ◽  
Author(s):  
Xia Yang ◽  
Xin Weng ◽  
Yajie Yang ◽  
Meng Zhang ◽  
Yingjie Xiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Gene Signature ◽  
Immune Gene

scholarly journals THER-06. GENOMIC AND IMMUNE CHARACTERIZATION OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i11-i12
Author(s):  
Benjamin Vincent ◽  
Maria Sambade ◽  
Shengjie Chai ◽  
Marni Siegel ◽  
Luz Cuaboy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Brain Metastases ◽  
T Cell Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Receptor ◽  
Gene Signature ◽  
Specific Response ◽  
Immune Gene

Abstract INTRODUCTION: Approximately 50% of patients with metastatic triple negative breast cancer (TNBC) will develop brain metastases (BM). Routinely treated with radiotherapy and/or surgery, survival is generally less than one year. There are no approved systemic therapies to treat TNBC BM. We characterized the genomic and immune landscape of TNBC BM to foster the development of effective brain permeable anti-cancer agents, including immunotherapy. EXPERIMENTAL PROCEDURES: A clinically-annotated BCBM biobank of archival tissues was created under IRB approval. DNA (tumor/normal) and RNA (tumor) were extracted from TNBC primaries and BM; whole exome (WES) and RNA sequencing (RNASeq) was performed. Mutations were determined from WES as those co-identified by two variant callers (Strelka|Cadabra). Immune gene signature expression, molecular subtype identification, and T cell receptor repertoires were inferred from RNAseq. RESULTS: 32 TNBC patient tissues (14 primaries, 18 BCBM, 6 primary-BCBM matched), characterized as basal-like by PAM50, were analyzed. Top exome mutation calls included ten genes in ≥19% of BCBMs including TP53, ATM, and PIK3R1, and four genes in ≥18% of primaries including TP53 and PIK3R1. Many immune gene signatures were lower in BM compared to primaries including B cell, dendritic cell, regulatory T cell, and IgG cluster (p< 0.05). A signature of PD-1 inhibition responsiveness was higher in BM compared with primaries (p< 0.05). BCBM T cell receptor repertoires showed higher evenness and lower read count (both p < 0.01) compared to primaries. CONCLUSIONS: TNBC BM compared to primaries that metastasize to the brain show lower immune gene signature expression, higher PD-1 inhibition response signature expression, and T cell receptor repertoire features less characteristic of an active antigen-specific response. Mutations common to TNBC BM and primaries include TP53 and PIK3R1. Given that non-BCBM (i.e. lung and melanoma) show response to checkpoint inhibitors, these findings collectively support further study of immunotherapy for TNBC BM.

scholarly journals Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5590
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Omar Salem ◽  
Yonghong Wan ◽  
Karen L. Mossman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Macrophage Polarization ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Differential Gene ◽  
Microarray Analyses ◽  
Tumor Cell Killing

The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing.

Risk stratification of triple-negative breast cancer with core gene signatures associated with chemoresponse and prognosis

2019 ◽  
Vol 178 (1) ◽  
pp. 185-197 ◽  
Author(s):  
Eun-Kyu Kim ◽  
Ae Kyung Park ◽  
Eunyoung Ko ◽  
Woong-Yang Park ◽  
Kyung-Min Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Core Gene ◽  
Gene Signatures

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer

2020 ◽  
Vol 184 (2) ◽  
pp. 325-334
Author(s):  
Ji-Yeon Kim ◽  
Hae Hyun Jung ◽  
Insuk Sohn ◽  
Sook Young Woo ◽  
Hyun Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Gene Signature ◽  
Related Gene ◽  
Immune Related Gene

scholarly journals A Six-Epithelial–Mesenchymal Transition Gene Signature May Predict Metastasis of Triple-Negative Breast Cancer

2020 ◽  
Vol Volume 13 ◽  
pp. 6497-6509
Author(s):  
Li Yuan Wei ◽  
Xiao Jun Zhang ◽  
Li Wang ◽  
Li Na Hu ◽  
Xu Dong Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Gene Signature ◽  
Mesenchymal Transition

Molecular characteristics and metastasis predictor genes of triple-negative breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1043-1043
Author(s):  
Wen-Hung Kuo ◽  
Yao-Yin Chang ◽  
Ming-Feng Hou ◽  
Eric Y Chuang ◽  
King-Jen Chang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Gene Signature ◽  
Breast Cancers ◽  
Prognostic Signature ◽  
Characteristic Analysis ◽  
Disease Etiology ◽  
Breast Cancer Outcome

1043 Background: Triple-negative breast cancer(TNBC) is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. Methods: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated with oligonucleotide microarrays. A prognostic 45-gene signature for triple-negative breast cancer was identified using Student’s t test and receiver operating characteristic analysis. Results: Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A novel 45-gene signature giving 98% predictive accuracy in distant metastasis recurrence was identified in our triple-negative patient cohort. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% CI 1.04-5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The prognostic signature was statistically predictive with the node-negative triple-negative patients in the validation cohort. Conclusions: The 45-gene prognostic signature identified in this study revealed that TGF-β signaling in immune/inflammatory regulation may be critically involved in distant metastatic invasion of TNBC. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of metastasis recurrence for early-stage triple-negative patients.

scholarly journals Interferon-beta represses cancer stem cell properties in triple-negative breast cancer

2017 ◽  
Vol 114 (52) ◽  
pp. 13792-13797 ◽  
Author(s):  
Mary R. Doherty ◽  
HyeonJoo Cheon ◽  
Damian J. Junk ◽  
Shaveta Vinayak ◽  
Vinay Varadan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Mammary Epithelial Cells ◽  
Gene Expression Signature ◽  
Tumor Infiltrating Lymphocytes ◽  
Gene Signature ◽  
Mesenchymal Transition

Triple-negative breast cancer (TNBC), the deadliest form of this disease, lacks a targeted therapy. TNBC tumors that fail to respond to chemotherapy are characterized by a repressed IFN/signal transducer and activator of transcription (IFN/STAT) gene signature and are often enriched for cancer stem cells (CSCs). We have found that human mammary epithelial cells that undergo an epithelial-to-mesenchymal transition (EMT) following transformation acquire CSC properties. These mesenchymal/CSCs have a significantly repressed IFN/STAT gene expression signature and an enhanced ability to migrate and form tumor spheres. Treatment with IFN-beta (IFN-β) led to a less aggressive epithelial/non–CSC-like state, with repressed expression of mesenchymal proteins (VIMENTIN, SLUG), reduced migration and tumor sphere formation, and reexpression of CD24 (a surface marker for non-CSCs), concomitant with an epithelium-like morphology. The CSC-like properties were correlated with high levels of unphosphorylated IFN-stimulated gene factor 3 (U-ISGF3), which was previously linked to resistance to DNA damage. Inhibiting the expression of IRF9 (the DNA-binding component of U-ISGF3) reduced the migration of mesenchymal/CSCs. Here we report a positive translational role for IFN-β, as gene expression profiling of patient-derived TNBC tumors demonstrates that an IFN-β metagene signature correlates with improved patient survival, an immune response linked with tumor-infiltrating lymphocytes (TILs), and a repressed CSC metagene signature. Taken together, our findings indicate that repressed IFN signaling in TNBCs with CSC-like properties is due to high levels of U-ISGF3 and that treatment with IFN-β reduces CSC properties, suggesting a therapeutic strategy to treat drug-resistant, highly aggressive TNBC tumors.

scholarly journals A Novel Platelet-Related Gene Signature for Predicting the Prognosis of Triple-Negative Breast Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Jindong Xie ◽  
Yutian Zou ◽  
Feng Ye ◽  
Wanzhen Zhao ◽  
Xinhua Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Clinical Prognosis

Regarded as the most invasive subtype, triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) proteins. Platelets have recently been shown to be associated with metastasis of malignant tumors. Nevertheless, the status of platelet-related genes in TNBC and their correlation with patient prognosis remain unknown. In this study, the expression and variation levels of platelet-related genes were identified and patients with TNBC were divided into three subtypes. We collected cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, we constructed a seven-gene signature which classified the two cohorts of patients with TNBC into low- or high-risk groups. Patients in the high-risk group were more likely to have lower survival rates than those in the low-risk group. The risk score, incorporated with the clinical features, was confirmed as an independent factor for predicting the overall survival (OS) time. Functional enrichment analyses revealed the involvement of a variety of vital biological processes and classical cancer-related pathways that could be important to the ultimate prognosis of TNBC. We then built a nomogram that performed well. Moreover, we tested the model in other cohorts and obtained positive outcomes. In conclusion, platelet-related genes were closely related to TNBC, and this novel signature could serve as a tool for the assessment of clinical prognosis.

scholarly journals 1q21.3 amplification modulates therapy sensitivity in Triple Negative Breast Cancer

2020 ◽  
Author(s):  
Ramakanth Chirravuri-Venkata ◽  
Dario Ghersi ◽  
Apar K. Ganti ◽  
Imayavaramban Lakshmanan ◽  
Sanjib Chaudary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Genetic Marker ◽  
Triple Negative Breast Cancer ◽  
Copy Number ◽  
Triple Negative ◽  
Copy Number Alterations ◽  
Copy Number Status ◽  
Cytotoxic Therapies

AbstractThe contrast in therapy sensitivity and response across triple negative breast cancer (TNBC) patients suggest underlying genotypic heterogeneity. Using publicly available data, we found significant associations between DNA-level copy number alterations of 1q21.3 locus and therapy sensitivity. We show that in spite of their aggressive nature, 1q21.3 amplified tumors are more responsive to commonly used cytotoxic therapies, highlighting the relevance of 1q21.3 copy number status as a genetic marker for risk stratification, therapy selection and response.

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