“…Some of the DEGs identified herein were also highly expressed in breast carcinoma cells, such as TFF3 (40) and AGR3 (35,41,42). Previous research suggests that TFF3 promotes angiogenesis in breast cancer (43), and AGR3 promotes the proliferation and migration of malignant breast cancer cells and functions in the resistance of breast carcinoma to tamoxifen (35,41,42). These results confirm the robustness of our analytic pipeline and enabled the identification of DEGs that play important roles in the development of breast carcinoma.…”
Section: Discussionsupporting
confidence: 82%
“…Notably, several novel genes that were highly expressed in breast cancer cells-H2AFJ and ARL61P1-have established functions in the resistance to cell proliferation in glioblastoma multiforme (38) and cervical cancer (39). Some of the DEGs identified herein were also highly expressed in breast carcinoma cells, such as TFF3 (40) and AGR3 (35,41,42). Previous research suggests that TFF3 promotes angiogenesis in breast cancer (43), and AGR3 promotes the proliferation and migration of malignant breast cancer cells and functions in the resistance of breast carcinoma to tamoxifen (35,41,42).…”
Background: Breast carcinoma is the most common malignancy among women worldwide. It is characterized by a complex tumor microenvironment (TME), in which there is an intricate combination of different types of cells, which can cause confusion when screening tumor-cell-related signatures or constructing a gene co-expression network. The recent emergence of single-cell RNA sequencing (scRNAseq) is an effective method for studying the changing omics of cells in complex TMEs.
Methods:The Dysregulated genes of malignant epithelial cells was screened by performing a comprehensive analysis of the public scRNA-seq data of 58 samples. Co-expression and Gene Set Enrichment Analysis (GSEA) analysis were performed based on scRNA-seq data of malignant cells to illustrate the potential function of these dysregulated genes. Iterative LASSO-Cox was used to perform a second-round screening among these dysregulated genes for constructing risk group. Finally, a breast cancer prognosis prediction model was constructed based on risk grouping and other clinical characteristics.Results: Our results indicated a transcriptional signature of 1,262 genes for malignant breast cancer epithelial cells. To estimate the function of these genes in breast cancer, we also constructed a co-expression network of these dysregulated genes at single-cell resolution, and further validated the results using more than 300 published transcriptomics datasets and 31 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening datasets. Moreover, we developed a reliable predictive model based on the scRNA-seq and bulk-seq datasets.Conclusions: Our findings provide insights into the transcriptomics and gene co-expression networks during breast carcinoma progression and suggest potential candidate biomarkers and therapeutic targets for the treatment of breast carcinoma. Our results are available via a web app (https://prognosticpredictor. shinyapps.io/GCNBC/).
“…Some of the DEGs identified herein were also highly expressed in breast carcinoma cells, such as TFF3 (40) and AGR3 (35,41,42). Previous research suggests that TFF3 promotes angiogenesis in breast cancer (43), and AGR3 promotes the proliferation and migration of malignant breast cancer cells and functions in the resistance of breast carcinoma to tamoxifen (35,41,42). These results confirm the robustness of our analytic pipeline and enabled the identification of DEGs that play important roles in the development of breast carcinoma.…”
Section: Discussionsupporting
confidence: 82%
“…Notably, several novel genes that were highly expressed in breast cancer cells-H2AFJ and ARL61P1-have established functions in the resistance to cell proliferation in glioblastoma multiforme (38) and cervical cancer (39). Some of the DEGs identified herein were also highly expressed in breast carcinoma cells, such as TFF3 (40) and AGR3 (35,41,42). Previous research suggests that TFF3 promotes angiogenesis in breast cancer (43), and AGR3 promotes the proliferation and migration of malignant breast cancer cells and functions in the resistance of breast carcinoma to tamoxifen (35,41,42).…”
Background: Breast carcinoma is the most common malignancy among women worldwide. It is characterized by a complex tumor microenvironment (TME), in which there is an intricate combination of different types of cells, which can cause confusion when screening tumor-cell-related signatures or constructing a gene co-expression network. The recent emergence of single-cell RNA sequencing (scRNAseq) is an effective method for studying the changing omics of cells in complex TMEs.
Methods:The Dysregulated genes of malignant epithelial cells was screened by performing a comprehensive analysis of the public scRNA-seq data of 58 samples. Co-expression and Gene Set Enrichment Analysis (GSEA) analysis were performed based on scRNA-seq data of malignant cells to illustrate the potential function of these dysregulated genes. Iterative LASSO-Cox was used to perform a second-round screening among these dysregulated genes for constructing risk group. Finally, a breast cancer prognosis prediction model was constructed based on risk grouping and other clinical characteristics.Results: Our results indicated a transcriptional signature of 1,262 genes for malignant breast cancer epithelial cells. To estimate the function of these genes in breast cancer, we also constructed a co-expression network of these dysregulated genes at single-cell resolution, and further validated the results using more than 300 published transcriptomics datasets and 31 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening datasets. Moreover, we developed a reliable predictive model based on the scRNA-seq and bulk-seq datasets.Conclusions: Our findings provide insights into the transcriptomics and gene co-expression networks during breast carcinoma progression and suggest potential candidate biomarkers and therapeutic targets for the treatment of breast carcinoma. Our results are available via a web app (https://prognosticpredictor. shinyapps.io/GCNBC/).
“…3 G), which have been associated with cancer cell progression and chemotherapy resistance [ 28 – 30 ]. Specifically, AGR3 promotes tamoxifen resistance in breast cancer [ 31 ], SRGN is a key molecule in mediating chemoresistance and stemness in breast cancer cells [ 30 ], and PPP1R1B is involved in resistance of breast cancer cells to trastuzumab [ 32 ]. Fig.…”
Background
Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity.
Methods
Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments.
Results
We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis.
Conclusions
This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer.
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