scholarly journals Upregulation of Long Non-Coding RNA DRAIC Correlates with Adverse Features of Breast Cancer

2018 ◽  
Vol 4 (4) ◽  
pp. 39 ◽  
Author(s):  
Dan Zhao ◽  
Jin-Tang Dong
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Non Coding Rna ◽  
Er Positive ◽  
Invasive Breast Carcinomas ◽  
Long Non Coding Rna

DRAIC (also known as LOC145837 and RP11-279F6.1), is a long non-coding RNA associated with several types of cancer including prostate cancer, lung cancer, and breast cancer. Its expression is elevated in tumor tissues compared to adjacent benign tissues in breast cancer patients and is regulated by estrogen treatment in breast cancer cells. In addition, expression analysis of DRAIC in more than 100 cell lines showed that DRAIC expression is high in luminal and basal subtypes compared to claudin low subtype, suggesting a prognostic value of DRAIC expression in breast cancer. In the present study, we analyzed DRAIC expression in 828 invasive breast carcinomas and 105 normal samples of RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and found that DRAIC expression was correlated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status, and is increased in cancerous tissues. Additionally, higher DRAIC expression was associated with poorer survival of patients, especially in ER positive breast cancer. DRAIC was also investigated in the Oncomine database and we found that DRAIC expression predicted patients’ response to paclitaxel and FEC as well as lapatinib, which are commonly used therapy options for breast cancer. Finally, DRAIC expression in breast cancer was negatively correlated with immune cell infiltration. These results reinforce the importance of DRAIC in breast cancer.

scholarly journals VWCE as a potential biomarker associated with immune infiltrates in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Her2 Status ◽  
Cancer Tissue ◽  
M2 Macrophage ◽  
Breast Cancer Patients ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Factor C

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

scholarly journals Biological subtypes and survival outcomes in breast cancer patients with brain metastases in the targeted therapy era

2017 ◽  
Vol 5 (3) ◽  
pp. 161-169 ◽  
Author(s):  
Dhiego Chaves de Almeida Bastos ◽  
Marcos Vinicius Calfat Maldaun ◽  
Raymond Sawaya ◽  
Dima Suki ◽  
Frederick F Lang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Brain Metastasis ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Cancer Center ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Molecular Features

Abstract Background There is recognition that breast cancer is a collection of heterogeneous diseases divided in subtypes based on combined molecular features such as hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status. We aimed to study clinical differences among biological subtypes in brain metastasis from breast cancer after targeted therapy introduction. Methods This was a retrospective study with 406 consecutive patients with brain metastasis from breast cancer treated at MD Anderson Cancer Center from 1998 to 2013. Overall, 315 of these patients met the study criteria and were analyzed. Subtypes were classified as HER2-/HR+ (96 patients), HER2+/HR+ (57 patients), HER2+/HR- (63 patients), and triple negative (HER2-/HR-) (99 patients). End points were time to development of brain metastasis (TDBM), brain metastasis-free survival (BMFS), and overall survival from start of treatment of brain metastasis (OSBM). Univariate and multivariate Cox proportional hazard regression models were used to analyze the data. Results TDBM was 41 months for HER2-/HR+; 58 months for HER2+/HR+; 30 months for HER2+/HR-; and 27 months for triple negative (P < .001). BMFS was 9 months for HER2-/HR+; 24 months for HER2+/HR+; 9 months for HER2+/HR-; and 7 months for triple negative (P = .06). OSBM was 20 months for HER2-/HR+; 22 months for HER2+/HR+; 24 months for HER2+/HR-; and 9 months for triple negative (P < .001). On multivariate analyses, triple negative showed lower OSBM compared with other subtypes, with a hazard ratio of 1.9 (P < .001). Conclusion Comparing all breast cancer subgroups we noticed that HR and HER2 are the most significant biomarkers in brain metastasis behavior. Patients who received targeted therapy had better outcomes, but not in the triple negative group. Prospective studies with different treatment modalities for each subgroup are recommended.

Clinically Used Breast Cancer Markers Such As Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Are Unstable Throughout Tumor Progression

2012 ◽  
Vol 30 (21) ◽  
pp. 2601-2608 ◽  
Author(s):  
Linda Sofie Lindström ◽  
Eva Karlsson ◽  
Ulla M. Wilking ◽  
Ulla Johansson ◽  
Johan Hartman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Tumor Progression ◽  
Patient Management ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Er Positive ◽  
Epidermal Growth

Purpose To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. Patients and Methods The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. Conclusion Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.

scholarly journals Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanghui Zhao ◽  
Junhua An ◽  
Qian Pu ◽  
Wenwen Geng ◽  
Haiyun Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients ◽  
Gene Signatures ◽  
Immune Phenotypes ◽  
Processing Stability

The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m6A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.

scholarly journals Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Huo ◽  
Siqi Chen ◽  
Zhenwei Li ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Coiled Coil ◽  
Growth Factor Receptor ◽  
Prognostic Index ◽  
Her2 Status ◽  
Breast Cancer Patients

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, nodal status, the scarff-bloom-richardson (SBR) grade, nottingham prognostic index (NPI), age, subtypes, and triple-negative and basal-like status, suggesting that TACC3 may be a potential diagnostic indicator of breast cancer. Furthermore, functional studies have shown that inhibition of TACC3 can significantly promote the cell proliferation and viability of breast cancer cells. Moreover, TACC3 knockdown suppressed the expression of E-cadherin, but increased the expression of N-cadherin, Snail, ZEB1, and TWIST, which indicate that TACC3 may impact the migration of breast cancer cells in vitro. Taken together, these findings indicate that TACC3 may serve as a prognostic and therapeutic indicator of breast cancer.

scholarly journals Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Peng-Ju Gong ◽  
You-Cheng Shao ◽  
Si-Rui Huang ◽  
Yi-Fan Zeng ◽  
Xiao-Ning Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Tumor Hypoxia ◽  
Gene Expression Signature ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Primary Tumors

ObjectiveMany primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer.Materials and MethodsAccording to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed.ResultsTwo subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as “hypoxic subgroup” compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the SNHG16-hsa-miR-210-3p-CPEB2 and LINC00899/PSMG3-AS1/PAXIP-AS1-hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively.ConclusionHypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.

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