Project description:Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study We used gene expression data of TNBC patients with residual disease and different prognosis to molecularly define the clinically relevant subgroups, and developed a 7-gene prognostic signature for chemoresistant TNBCs
Project description:Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study
Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.
Project description:In this study, we analyzed the differential spatial transcriptome of Triple-Negative Breast Cancer (TNBC) patients who responded in an opposite manner to neoadjuvant chemotherapy (NACT): we compared responders displaying pathological complete response (pCR) with no-responders who showed disease progression during therapy. Diagnostic TruCut biopsies were analyzed using the GeoMx Cancer Transcriptome Atlas (Nanostring).
Project description:Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC), which exhibited a poor prognosis due to the highly tumor microenvironmental heterogeneity and specific mutations. Recent studies have investigated the different celltypes in TNBC microenvironment, however, the effects of immunotherapy and chemotherapy combination therapy on TNBC are largely unknown. Here we explored the changes of TNBC microenvironment upon immunotherapy and chemotherapy combination therapy by scRNA-seq. We found that the insensitive (PCPAi) patient exhibited high CNV score in tumor cells, lower cytotoxicity in CD8+ T cells, higher quiescence and exhaustion characteristics CD4+ T cells, compared to sensitive (PCPAs) patient. Meanwhile, the PCPAi patient showed more complex fibroblasts and tumor-associated macrophages heterogeneity. We also found the key ligand-receptor based cellular interactions, such as SPP1 and TGFβ. These results provide a research basis for us to understand the microenvironment changes and therapeutic efficacy of triple negative breast cancer after chemotherapy combined with immunotherapy.
Project description:An TMT-based quantitative phosphoproteome analysis using liquid chromatography–coupled tandem mass spectrometry was performed to acquire proteome-wide expression data on Triple-negative Breast Cancer (TNBC) cells treated with time-course Rocaglamide A.