Project description:We thoroughly analyzed the molecular subtyping of Triple-Negative Breast Cancer and its different manifestations, and located T cells and Tumor cells related to the survival of breast cancer through single cell sequencing and space transcriptome according to our score, and finally investigated their relationship with the therapeutic efficacy, providing a scientific basis for the treatment of triple negative breast cancer.
Project description:We thoroughly analyzed the molecular subtyping of Triple-Negative Breast Cancer and its different manifestations, and located T cells and Tumor cells related to the survival of breast cancer through single cell sequencing and space transcriptome according to our score, and finally investigated their relationship with the therapeutic efficacy, providing a scientific basis for the treatment of triple negative breast cancer.
Project description:Triple-negative breast cancer (TNBC) is considered the most aggressive type of breast cancer with limited options for therapy. TNBC is a heterogeneous disease and tumours has been classified into TNBC subtypes using gene expression profiling to distinguish basal-like1 (BL1), basal-like2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal/stem-like (MSL), luminal androgen receptor (LAR) and one non-classifiable group (called unstable, UNS). The aim of this study was to verify the clinical relevance of molecular subtyping of TNBCs by expression analysis to improve the individual indication of systemic therapy.
Project description:Triple negative breast cancers lack targeted therapies with little side effects and contain higher percentage of cancer stem cells than the other breast cancer subtypes. Genes capturing the features of cancer stem cells of such diseases may serve as potential subtyping marker or therapeutic targets for triple negative breast cancer management. This data descriptor presents a set of transcriptome data from 3 cohorts of cancer stem cells as represented as CD44+/CD24-/low and 2 cohorts of non-cancer stem cells isolated from triple negative breast cancer cells, each having 3 replicates.
Project description:Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients. We conducted an unsupervised analysis of microarray gene-expression profiles of 107 TN breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. An 87 TN external cohort was used for validation. Fuzzy clustering separated TN tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P < 0.0001 for both comparisons). Significant event-free survival (EFS) (P = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 (P = 0.01) and C2 (P = 0.02). EFS analysis results were confirmed when our cohort was pooled with external cohort (n = 194; P = 0.01). Functional annotation showed that 22% of TN patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor [LAR]). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes, but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response (HIR) and low M2-like macrophages were a hallmark of C3, and that these patients had a better EFS than C2 patients, characterized by low immune response (LIR) and high M2-like macrophages: P = 0.02 for our cohort, and P = 0.03 for pooled cohorts. We identified 3 subtypes of TN patients: LAR (22%), basal-like with LIR and high M2-like macrophages (45%) and basal-enriched with HIR and low M2-like macrophages (33%). We pointed out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in TN basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype TN patients. Subtyping molecular characterization within a cohort of 107 TN-IHC by means of gene expression profiling
Project description:Molecular subtyping plays a vital role in the treatment of breast cancer, however, current clinical outcomes remain unsatisfactory despite having multiple molecular subtypes available, particularly for triple-negative breast cancers. Henceforth, our research primarily focuses on traditional molecular subtyping by utilizing transcriptome sequencing and ATAC-seq sequencing techniques to classify both tumor tissues and adjacent tissues from patients with breasts cancers into distinct groups. Through this process, we aim to identify key gene expressions involved in the development of breasts cancers as well as epigenetic characteristics influenced by alterations in chromatin accessibility patterns. Subsequently, employing conventional methods used for classifying breasts cancers into different molecular types enables us to further investigate significant variations observed specifically within triple-negative breasts cancers regarding their gene expression profiles and chromatin accessibility patterns. Lastly, utilizing data from TCGA database pertaining exclusively to cases involving triple-negative breasts cancers allows us to conduct regression analyses concerning our aforementioned findings while simultaneously selecting relevant molecular models closely associated with this particular subtype of breasts malignancy. Additionally evaluating how these differentially expressed genes influence prognosis through prognostic modeling analysis tailored towards predicting outcomes solely within cases involving individuals diagnosed with triple negative-breast malignancies will enable us ultimately construct an innovative model incorporating both gene expressions along with chromatin accessibility patterns as distinguishing features providing more substantial guidance towards improving clinical treatments targeting individuals afflicted by such conditions.
Project description:This study developed a triple-negative breast cancer (TNBC) surrogate subtype classification that represents TNBC subtypes based on the Vanderbilt subtype classification The web-based subtyping tool TNBCtype was used to classify the TNBC cohort into Vanderbilt subtypes
