scholarly journals Expression and Gene Regulation Network of Metabolic Enzyme Phosphoglycerate Mutase Enzyme 1 in Breast Cancer Based on Data Mining

2021 ◽  
Vol 2021 ◽  
pp. 1-39
Author(s):  
Yongxuan Wang ◽  
Xifeng Xiong ◽  
Xing Hua ◽  
Wei Liu
Keyword(s):  
Breast Cancer ◽  
Data Mining ◽  
Transcription Factors ◽  
Cancer Progression ◽  
Molecular Subtype ◽  
Expression Level ◽  
Phosphoglycerate Mutase ◽  
Metabolic Enzyme ◽  
Sequencing Data ◽  
Her2 Positive

The metabolic enzyme phosphoglycerate mutase enzyme 1 (PGAM1) is a key enzyme in the glycolysis pathway, and glycolysis is closely related to cancer progression, suggesting that PGAM1 may have important functions in breast cancer. We used sequencing data from the Oncomine database and UALCAN database to analyze the expression of PGAM1 and its influence on the clinicopathological characteristics of breast cancer. LinkedOmics was used to identify genes related to PGAM1 expression, kinases, miRNAs, and transcription factors that were significantly related to PGAM1 through GSEA. cBioPortal was used to identify the alternation frequency and form of PGAM1 in breast cancer. The expression level of PGAM1 in breast cancer was significantly higher than that in normal tissues. Moreover, the expression level of PGAM1 is closely related to the molecular subtype and TP53 mutation status. The expression level of PGAM1 in HER2-positive and triple-negative tumors was significantly higher than that of luminal type. The expression level of PGAM1 in TP53-mutant tumors was higher than that in non-TP53-mutant tumors. In addition, the overall survival of patients with high PGAM1 expression was significantly worse than that of patients with low expression ( P = 0.0077 ). Through GSEA analysis, we found multiple kinases, miRNAs, and transcription factors significantly related to PFKFB4. cBioPortal analysis showed that the mutation rate of PGAM1 in breast cancer was relatively low (4%), and the main form of mutation was high mRNA expression. This study suggests that PGAM1 is a potential diagnostic and prognostic marker in breast cancer. Through data mining, we revealed the potential regulatory network information of PGAM1, laying a foundation for further research on the role of PGAM1 in breast cancer.

scholarly journals Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Her2 Positive ◽  
Pathway Gene ◽  
Dual Specificity ◽  
The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

scholarly journals Centromere 17 copy number gain reflects chromosomal instability in breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyoungyul Lee ◽  
Hyun Jeong Kim ◽  
Min Hye Jang ◽  
Sejoon Lee ◽  
Soomin Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Chromosomal Instability ◽  
Copy Number Gain ◽  
Next Generation Sequencing Data ◽  
Her2 Status ◽  
Sequencing Data ◽  
Her2 Positive ◽  
Ki 67 ◽  
Positive Linear Correlation

AbstractChromosomal instability (CIN) is known to be associated with prognosis and treatment response in breast cancer. This study was conducted to determine whether copy number gain of centromere 17 (CEP17) reflects CIN, and to evaluate the prognostic and predictive value of CIN in breast cancer. CIN status was determined by summing copy number gains of four centromeric probes (CEP1, CEP8, CEP11, and CEP16) based on fluorescence in situ hybridization and CIN scores were calculated using next generation sequencing data. High CIN was associated with adverse clinicopatholgical parameters of breast cancer. Among them, positive HER2 status, high Ki-67 index and CEP17 copy number gain were found to be independent predictors of high CIN. High CIN was associated with poor clinical outcome of the patients in the whole group, as well as in luminal/HER2-negative and HER2-positive subtypes. CEP17 copy number was significantly higher in the high-CIN-score group than in the low-CIN-score group. A positive linear correlation between the mean CEP17 copy number and the CIN score was found. In conclusion, CEP17 copy number was confirmed as a useful predictor for CIN in breast cancer, and high CIN was revealed as an indicator of poor prognosis in breast cancer.

scholarly journals Optimization of Taste-Masked (–)-Oleocanthal Effervescent Formulation with Potent Breast Cancer Progression and Recurrence Suppressive Activities

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 515 ◽  
Author(s):  
Tajmim ◽  
Siddique ◽  
El Sayed
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Locoregional Recurrence ◽  
Virgin Olive Oil ◽  
Xenograft Model ◽  
Taste Masking ◽  
Control Group ◽  
Placebo Control ◽  
Her2 Positive ◽  
Mouse Xenograft Model

S-(–)-Oleocanthal (OC), a naturally occurring phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO), is a potential nutraceutical therapeutic for inflammation, neurodegenerative diseases, and many malignancies, especially breast cancer (BC). The oral delivery of OC is challenging because of its irritative, bitter, and pungent taste and exceptional chemistry, including two reactive aldehydes, phenolic, and ester groups. OC irritation did not correlate with CO2-induced irritation, and hence, OC was not exerting generalized acid-sensing irritation. The objective of this study was to develop an effervescent formulation of OC with an effective CO2-induced masked taste maintaining the efficacy against the estrogen receptor (ER) and HER2 positive BC. Several ratios of acid and carbonate sources were screened, and five effervescent formulations EF1-EF5 were selected and prepared based on their pH and effervescence time. OC formulations were characterized using differential scanning calorimetry, FT-IR spectroscopy, and scanning electron microscopy analyses. OC formulations exhibited acceptable flowability and effervescence time. Based on physical characteristics and improved OC release, formulation EF-2 was selected for subsequent studies. EF-2 showed effective OC taste masking, as suggested by electronic artificial tongue and mouse preference tests. EF-2 suppressed more than 70% of the hormone and HER2-positive BT-474 BC cell growth in a nude mouse xenograft model. Furthermore, EF-2 demonstrated significant inhibition of BT-474 tumor cell locoregional recurrence after primary tumor surgical excision. EF-2-treated mouse sera had significantly reduced CA 15-3 levels, the human BC recurrence marker, compared to the placebo control group at the end of the study. These results highlight the potential of the OC formulation EF-2 as a prospective nutraceutical for the control and prevention of ER+/HER+ BC progression and locoregional recurrence.

Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer

2013 ◽  
pp. e2-e11
Author(s):  
Dimitrios Zardavas ◽  
David Cameron ◽  
Ian Krop ◽  
Martine Piccart
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Molecular Subtype ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Clinical Issue ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Positive Breast Cancer

HER2-positive breast cancer (BC) constitutes a molecular subtype of the disease with an aggressive biologic behavior. Trastuzumab revolutionized the treatment of this disease, changing its natural history. Lapatinib is active in the metastatic setting, approved for patients who were pretreated with trastuzumab. However, resistance to anti-HER2 agents is a major clinical issue, occurring in both early-stage and advanced disease, and new treatment options are clearly needed. An abundance of HER2-targeted agents are being clinically developed: monoclonal antibodies, small molecule inhibitors, and antibody drug conjugates (ADC). Combining HER2-targeted agents in regimens of dual HER2 blockade has already reached clinical practice in the metastatic setting, confirming the preclinical efficacy of enhanced HER2 inhibition. Promising results have been generated in the neoadjuvant setting, and large randomized trials are seeking evidence for dual HER2 blockade in the adjuvant setting. ADC represent another hope for improved treatment outcomes of HER2-positive BC, as exemplified by the positive results of clinical trials employing trastuzumab-DM1 (trastuzumab emtansine, T-DM1). Moreover, an understanding of the molecular mechanisms mediating resistance to HER2 blockade has opened new therapeutic avenues, with several targeted agents entering clinical trials. This paper presents the clinical data of the HER2-targeted agents under development, as well as an overview of the biologic rationale for the development of agents aimed at circumventing anti-HER2 resistance.

Breast cancer in Angola, molecular subtypes: The first preliminary study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Locally Advanced ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Therapeutic Decisions ◽  
Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

scholarly journals Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

2017 ◽  
Vol 44 (5) ◽  
pp. 1741-1748 ◽  
Author(s):  
Xiu Juan Li ◽  
Zhao Jun Ren ◽  
Jin Hai Tang ◽  
Qiao Yu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Functional Significance ◽  
Metastatic Breast ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Cell Viability Assay ◽  
Exosomal Mirnas ◽  
Exosomal Microrna

Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

scholarly journals Establishment and Characterization of a HER2-Positive Cell Line Derived From the Pleural Effusion of a Drug-Resistant Breast Cancer Patient

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhaoqing Li ◽  
Wenying Zhuo ◽  
Lini Chen ◽  
Xun Zhang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pleural Effusion ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Cell Line ◽  
Cell Lines ◽  
Molecular Subtype ◽  
Metastatic Breast ◽  
Drug Resistant ◽  
Her2 Positive

Drug resistance is a daunting challenge in the treatment of breast cancer, making it an urgent problem to solve in studies. Cell lines are important tools in basic and preclinical studies; however, few breast cell lines from drug-resistant patients are available. Herein, we established a novel HER2-positive breast cancer cell line from the pleural effusion of a drug-resistant metastatic breast cancer patient. This cell line has potent proliferative capability and tumorigenicity in nude mice but weak invasive and colony-forming capability. The molecular subtype of the cell line and its sensitivity to chemotherapeutics and HER2-targeting agents are different from those of its origin, suggesting that the phenotype changes between the primary and metastatic forms of breast cancer.

scholarly journals Association Analysis of Obesity/Overweight and Breast Cancer Using Data Mining Techniques

2021 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Mahsa Dehghani Soufi ◽  
Reza Ferdousi
Keyword(s):  
Breast Cancer ◽  
Data Mining ◽  
Hierarchical Clustering ◽  
Cancer Progression ◽  
Clustering Algorithm ◽  
Breast Cancer Incidence ◽  
Research Work ◽  
Model Assessment ◽  
Cancer Data ◽  
Data Mining Algorithms

Introduction: Growing evidence has shown that some overweight factors could be implicated in tumor genesis, higher recurrence and mortality. In addition, association of various overweight factors and breast cancer has not been extensively explored. The goal of this research was to explore and evaluate the association of various overweight/obesity factors and breast cancer, based on obesity breast cancer data set.Material and Methods: Several studies show that a significantly stronger association is obvious between overweight and higher breast cancer incidence, but the role of some overweight factors such as BMI, insulin-resistance, Homeostasis Model Assessment (HOMA), Leptin, adiponectin, glucose and MCP.1 is still debatable, So for experiment of research work several clinical and biochemical overweight factors, including age, Body Mass Index (BMI), Glucose, Insulin, Homeostatic Model Assessment (HOMA), Leptin, Adiponectin, Resistin and Monocyte chemo attractant protein-1(MCP-1) were analyzed. Data mining algorithms including k-means, Apriori, Hierarchical clustering algorithm (HCM) were applied using orange version 3.22 as an open source data mining tool.Results: The Apriori algorithm generated a list of frequent item sets and some strong rules from dataset and found that insulin, HOMA and leptin are two items often simultaneously were seen for BC patients that leads to cancer progression. K-means algorithm applied and it divided samples on three clusters and its results showed that the pair of andlt;Adiponectin, MCP.1andgt;  has the highest effect on seperation of clusters. In addition HCM was carried out and classified BC patients into 1-32 clusters to So this research apply HCM algorithm. We carried out hierarchical clustering with average linkage without purning and classified BC patients into 1–32 clusters in order to identify BC patients with similar charestrictics.Conclusion: These finding provide the employed algorithms in this study can be helpful to our aim.

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