scholarly journals The Hedgehog transcription factor GLI3 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab, a monoclonal antibody that targets HER2, is utilized for the treatment of breast cancer (1). While the mechanism of action of trastuzumab function in breast cancer is ascribed to trastuzumab binding to the extracellular region of HER2 (2), the transcriptional consequences that follow this binding event are less well understood. We report here, using analysis of published microarray and gene expression data (3, 4), that the transcription factor GLI3 (5) is differentially expressed in the tumors of patients with breast cancer treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab, a monoclonal antibody that targets HER2, is utilized for the treatment of breast cancer (1). While the mechanism of action of trastuzumab function in breast cancer is ascribed to trastuzumab binding to the extracellular region of HER2 (2), the transcriptional consequences that follow this binding event are less well understood. We report here, using analysis of published microarray and gene expression data (3, 4), that the gene encoding the E3 ubiquitin ligase Casitas B-lineage Lymphoma, CBL (5-8), is differentially expressed in the tumors of patients with breast cancer treated with trastuzumab. These data demonstrate that a bona fide proto-oncogene is expressed at higher levels in the primary tumors of trastuzumab-treated patients with breast cancer.


2020 ◽  
Vol 15 ◽  
Author(s):  
Chen-An Tsai ◽  
James J. Chen

Background: Gene set enrichment analyses (GSEA) provide a useful and powerful approach to identify differentially expressed gene sets with prior biological knowledge. Several GSEA algorithms have been proposed to perform enrichment analyses on groups of genes. However, many of these algorithms have focused on identification of differentially expressed gene sets in a given phenotype. Objective: In this paper, we propose a gene set analytic framework, Gene Set Correlation Analysis (GSCoA), that simultaneously measures within and between gene sets variation to identify sets of genes enriched for differential expression and highly co-related pathways. Methods: We apply co-inertia analysis to the comparisons of cross-gene sets in gene expression data to measure the costructure of expression profiles in pairs of gene sets. Co-inertia analysis (CIA) is one multivariate method to identify trends or co-relationships in multiple datasets, which contain the same samples. The objective of CIA is to seek ordinations (dimension reduction diagrams) of two gene sets such that the square covariance between the projections of the gene sets on successive axes is maximized. Simulation studies illustrate that CIA offers superior performance in identifying corelationships between gene sets in all simulation settings when compared to correlation-based gene set methods. Result and Conclusion: We also combine between-gene set CIA and GSEA to discover the relationships between gene sets significantly associated with phenotypes. In addition, we provide a graphical technique for visualizing and simultaneously exploring the associations of between and within gene sets and their interaction and network. We then demonstrate integration of within and between gene sets variation using CIA and GSEA, applied to the p53 gene expression data using the c2 curated gene sets. Ultimately, the GSCoA approach provides an attractive tool for identification and visualization of novel associations between pairs of gene sets by integrating co-relationships between gene sets into gene set analysis.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gaia Griguolo ◽  
Maria Vittoria Dieci ◽  
Laia Paré ◽  
Federica Miglietta ◽  
Daniele Giulio Generali ◽  
...  

AbstractLittle is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2− breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2− early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).


2000 ◽  
Vol 16 (8) ◽  
pp. 685-698 ◽  
Author(s):  
E. Manduchi ◽  
G. R. Grant ◽  
S. E. McKenzie ◽  
G. C. Overton ◽  
S. Surrey ◽  
...  

2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified myelin transcription factor 1, encoded by MYT1 among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of MYT1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of MYT1 in primary tumors of the breast, demonstrating increased expression of a zinc finger DNA-binding protein and neuronal-specific members of the LSD1 complex with the capacity to interact with Sin3B and with functions in neurogenesis (5-9) as a direct transcriptional consequence of treatment with trastuzumab.


Methods ◽  
2020 ◽  
Vol 179 ◽  
pp. 89-100 ◽  
Author(s):  
Kyuri Jo ◽  
Beatriz Santos-Buitrago ◽  
Minsu Kim ◽  
Sungmin Rhee ◽  
Carolyn Talcott ◽  
...  

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