scholarly journals High MYC mRNA Expression Is More Clinically Relevant than MYC DNA Amplification in Triple-Negative Breast Cancer

2019 ◽  
Vol 21 (1) ◽  
pp. 217 ◽  
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Takashi Takeshita ◽  
Kerry-Ann McDonald ◽  
Subhamoy Dasgupta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Triple Negative Breast Cancer ◽  
Target Genes ◽  
Triple Negative ◽  
Dna Amplification ◽  
High Expression ◽  
Inclusion Criteria ◽  
Gene Sets ◽  
The Difference

DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting that MYC DNA amplification does not always result in elevated MYC mRNA expression. Compared to other subtypes, both MYC DNA amplification and mRNA high expression were more frequent in the TNBCs. MYC mRNA high expression, but not DNA amplification, was significantly associated with worse overall survival in the TNBCs. The TNBCs with MYC mRNA high expression enriched MYC target genes, cell cycle related genes, and WNT/β-catenin gene sets, whereas none of them were enriched in MYC DNA amplified TNBCs. In conclusion, MYC mRNA high expression, but not DNA amplification, reflects not only its upregulated signaling pathway, but also clinical significance in TNBCs.

scholarly journals Expression of MxA Protein in Triple Negative Breast Cancer and its Relationship with Prognosis

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Jinmei Li ◽  
Jirui Sun ◽  
Hong Chen ◽  
Qiushuang Ma ◽  
Jinku Zhang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Protein A ◽  
Disease Free Survival ◽  
High Expression ◽  
Free Survival ◽  
High Expression Group ◽  
The Difference ◽  
Breast Tissues

Objective: To explore the expression of human myxovirus resistance protein A (MxA) in triple negative breast cancer (TNBC) and its relationship with prognosis. Methods: 144 cases of TNBC confirmed by pathology before or after surgery from January 2014 to January 2017 in the First Central Hospital of Baoding City were retrospectively collected. Western blotting was used to detect the expression of MxA protein in TNBC and adjacent breast tissues. According to the expression of MxA protein, 144 TNBC patients were divided into low MxA protein expression group (n = 91) and MxA protein high expression group (n = 53) for subsequent comparison of prognosis of patients in between these two groups. Results: The expression of MxA protein in TNBC tissue was lower than that of adjacent breast tissue, and the difference was statistically significant (P<0.05). The patients in high MxA expression group had higher loco-regional recurrence-free rate, disease-free survival (DFS) rate, and overall survival (OS) rate than those in low MxA expression group for 3 years. On the other hand, the distant metastasis rate was lower in the high expression group compared to that in the low MxA expression group, and the difference was statistically significant (P<0.05). Conclusion: In triple-negative breast cancer, high MxA expression is a potential predictor of TNBC prognosis.

scholarly journals TBC1D9: An Important Modulator of Tumorigenesis in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3557
Author(s):  
Charu Kothari ◽  
Alisson Clemenceau ◽  
Geneviève Ouellette ◽  
Kaoutar Ennour-Idrissi ◽  
Annick Michaud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Effective Treatment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Study Analysis ◽  
Tumor Aggressiveness ◽  
Domain Family ◽  
Proliferative Index ◽  
Tumorigenic Potential ◽  
The Difference

Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.

scholarly journals IGF-1/IGF-1R/FAK/YAP Transduction Signaling Prompts Growth Effects in Triple-Negative Breast Cancer (TNBC) Cells

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1010 ◽  
Author(s):  
Damiano Cosimo Rigiracciolo ◽  
Nijiro Nohata ◽  
Rosamaria Lappano ◽  
Francesca Cirillo ◽  
Marianna Talia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Triple Negative ◽  
Cancer Genomics ◽  
Treatment Options ◽  
Signal Transduction Pathway ◽  
Growth Potential ◽  
Nuclear Accumulation

Triple-negative breast cancer (TNBC) is an aggressive breast tumor subtype that currently lacks targeted treatment options. The role played by the insulin-like growth factor-1 (IGF-1) and its cognate receptor IGF-1R in TNBC has been reported. Nevertheless, the molecular mechanisms by which the IGF-1/IGF-1R system may contribute to TNBC progression still remains to be fully understood. By computational analysis of the vast cancer genomics information in public databases (TCGA and METABRIC), we obtained evidence that high IGF-1 or IGF-1R levels correlate with a worse clinical outcome in TNBC patients. Further bioinformatics analysis revealed that both the focal adhesion and the Hippo pathways are enriched in TNBC harboring an elevated expression of IGF-1 or IGF-1R. Mechanistically, we found that in TNBC cells, the IGF-1/IGF-1R system promotes the activation of the FAK signal transduction pathway, which in turn regulates the nuclear accumulation of YAP (yes-associated protein/yes-related protein) and the expression of its target genes. At the biological level, we found that the IGF-1/IGF-1R-FAK-YAP network cascade triggers the growth potential of TNBC cells, as evaluated in different experimental systems. Overall, our results suggest that the IGF-1/IGF-1R/FAK/YAP axis may contribute to the progression of the aggressive TNBC subtype.

scholarly journals High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients

2012 ◽  
Vol 30 (1) ◽  
Author(s):  
Shu Zhao ◽  
Wenjie Ma ◽  
Minghui Zhang ◽  
Dabei Tang ◽  
Qingtao Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
High Expression
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