scholarly journals Expression Pattern and Prognostic Value of EPHA/EFNA in Breast Cancer by Bioinformatics Analysis: Revealing Its Importance in Chemotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Zheng Liang ◽  
Xu Wang ◽  
Kaiti Dong ◽  
Xinhua Li ◽  
Chenge Qin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Expression Pattern ◽  
Prognostic Value ◽  
Genetic Alterations ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Poor Overall Survival

The activities of the ephrin family in breast cancer (BrCa) are complex. Family A receptors (EPHA) and ligands (EFNA) can act as oncogenes or tumor suppressors and are implicated in chemoresistance. Here, we examined the expression pattern and prognostic value of the EPHA/EFNA family in patients with breast cancer, including patients with different subtypes or different chemotherapy cohorts. In the UALCAN database, the mRNA expression of EPHA1, EPHA10, EFNA1, EFNA3, and EFNA4 was significantly higher, whereas that of EPHA2, EPHA4, EPHA5, and EFNA5 was significantly lower in breast cancer tissues than in paracancerous tissues. The transcriptional levels of EPHA/EFNA family members were correlated with intrinsic subclasses of breast cancer. The relationship between EPHA/EFNA and the clinicopathological parameters of BrCa was analyzed using bc-GenExMiner V4.5. EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 were upregulated in estrogen receptor- (ER-) and progesterone receptor- (PR-) negative tumors, whereas EPHA3, EPHA6, and EFNA1 were upregulated in ER- and PR-positive tumors. EPHA1, EPHA2, EFNA3, and EFNA4 mRNA expression was significantly higher in human epidermal growth factor receptor 2- (HER2-) positive tumors than in HER2-negative tumors. Triple-negative status was positively correlated with EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 and negatively correlated with EPHA3 and EPHA10 mRNA expression. Genetic alterations of EPHA/EFNA in breast cancer varied from 1.1% to 10% for individual genes, as determined by the cBioPortal database. The Kaplan–Meier plotter indicated that high EphA7 mRNA expression was associated with poor overall survival (OS) and recurrence-free survival (RFS), especially in the HER2 and luminal A subtypes. EFNA4 was predicted to have poor OS and RFS in breast cancers, especially in luminal B, basal-like subtype, and patients treated with adjuvant chemotherapy. High EPHA3 expression was significantly associated with better OS and RFS, especially in the luminal A subtype, but with poor RFS in BrCa patients receiving chemotherapy. Our findings systematically elucidate the expression pattern and prognostic value of the EPHA/EFNA family in BrCa, which might provide potential prognostic factors and novel targets in BrCa patients, including those with different subtypes or treated with chemotherapy.

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

Abstract Background: Breast cancer is the most commonly malignant cancers in women, and BIRC5 has been found to be overexpressed in a variety of human tumors. Its expression is associated with the prognosis of many cancers. However, whether BIRC5 mRNA could be used as an independent prognostic factor for breast cancer remains inconsistent in previous studies.Methods: Altered BIRC5 expression in normal tissue relative to various tumor tissue and in breast cancer patients with different molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO and Kaplan-Meier plotter datasets.Results: We found that many breast cancers had increased BIRC5 mRNA expression, and GOBO analysis showed that triple-negative cell lines displayed highest BIRC5 mRNA expression levels in the breast cancer cell line panel. Moreover, BIRC5 high mRNA expression was significantly associated with longer relapse-free survival (RFS) in all breast cancer patients. In particular, sub analysis revealed that high mRNA expression of BIRC5 was significantly associated with better survival in ER positive (HR = 2.05, p = 1e-16), but not in ER negative breast cancer (HR = 1.24, p = 0.1), furthermore, the results also demonstrated that BIRC5 high expression was significantly associated with longer RFS in luminal A (HR = 1.51, p = 3.1e-06) and luminal B (HR = 1.28, p = 0.026).Conclusions: In conclusion, BIRC5 is involved in the development and progression of breast cancer and may be a suitable prognostic marker for human breast cancer.

scholarly journals Deletion of the PER3 Gene on Chromosome 1p36 in Recurrent ER-Positive Breast Cancer

2010 ◽  
Vol 28 (23) ◽  
pp. 3770-3778 ◽  
Author(s):  
Joan Climent ◽  
Jesus Perez-Losada ◽  
David A. Quigley ◽  
Il-Jin Kim ◽  
Reyno Delrosario ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Recurrence ◽  
Gene Copy Number ◽  
Genetic Alterations ◽  
Gene Copy ◽  
Breast Cancers ◽  
Breast Tumorigenesis ◽  
Luminal A ◽  
Er Positive ◽  
Chromosome 1P36

Purpose To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development. Patients and Methods The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node–negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer. Results Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) – positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2. Conclusion Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.

scholarly journals Over-expression of SRD5A3 and its prognostic significance in breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yong-ping Zhang ◽  
Wen-ting Na ◽  
Xiao-qiang Dai ◽  
Ruo-fei Li ◽  
Jian-xiong Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Cox Regression Analysis ◽  
Expression Levels

Abstract Objective The study aimed to compare the Steroid 5 alpha-reductase 3 (SRD5A3) expression levels in breast cancer (BC) and normal tissues, to investigate the prognostic value of SRD5A3 mRNA expression in BC patients and to identify the SRD5A3-related signaling pathways using bioinformatics approaches. Methods We evaluated the expression levels of SRD5A3 and survival data in BC patients using different bioinformatic databases. Further, Cox regression analysis was conducted to predict the independent prognostic factors for BC. Moreover, the association of SRD5A3 with clinicopathological factors was measured through LinkedOmics database. And the potential role of SRD5A3 was determined by Gene Ontology and KEGG pathway enrichment analysis. Finally, protein network of SRD5A3 was constructed and genetic alterations were analyzed. Results Bioinformatic data indicated that both mRNA and protein expression levels of SRD5A3 were higher in BC group than those in the normal group (P < 0.05). Besides, BC patients with higher SRD5A3 mRNA expression levels had a lower overall survival (all P < 0.05). Cox regression analysis further demonstrated the independent prognostic value of SRD5A3 in BC (P = 0.015). SRD5A3 mRNA expression was significantly associated with N stage (P < 0.001), age (P < 0.05), and histologic subtype (P < 0.001) but had no significant relationship with other clinical characteristics (all P > 0.05). Moreover, the functional enrichment analysis revealed that the SRD5A3 was involved in metabolism-related pathways (all P < 0.05). Conclusions SRD5A3 was highly expressed in BC tissues and high SRD5A3 expression was related to poorer prognosis. SRD5A3 serves as an oncogene and might function as a potential biomarker for prognosis and a therapeutic target for BC.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

scholarly journals O80: GREMLIN-1 PROMOTES TUMOURIGENESIS AND METASTASIS IN HER2 POSITIVE BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
C Zabkiewicz ◽  
L Ye ◽  
R Hargest
Keyword(s):  
Breast Cancer ◽  
Cellular Growth ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Her2 Breast Cancer ◽  
Bmp Signalling ◽  
Gremlin 1

Abstract Introduction HER2 over-expression denotes poor prognosis in breast cancers.Bone morphogenetic protein(BMP) signalling is known to interact with EGF signalling, co-regulating breast cancer progression.BMP antagonist Gremlin-1 may influence breast cancer disease progression, but this remains unexplored in HER2 positive breast cancers. Method GREM1 and HER2 expression, and clinical outcomes were examined in clinical cohorts.GREM1 overexpression or pEF control plasmid were transduced into BT474 HER2+breast cancer cells. In vitro function tests using BT474 pEF and BT474GREM1cells include 2D/3D growth, migration, and expression of epithelial to mesenchymal transition(EMT)markers. Signalling cascades were examined in BT474 treated with RhGremlin-1. In vivo, BALB/c nude mice underwent either mammary injection or intra-cardiac injection of BT474pEF or BT474GREM1 cells and disease burden assessed. Result GREM1 expression correlates with HER2 in breast tumours(p=0.03) and is higher in metastatic HER2 positive cancers (p = 0.04). HER2 positive patients with high GREM1 have poor survival(p = 0.0002). BT474GREM1cells have up-regulated markers of EMT compared to control. BT474 RhGremlin-1 treated cells have active AKT pathway signalling, independent of BMP signalling. In vitro,  BT474GREM1cells significantly proliferate and migrate compared to control(p&lt;0.05 and p &lt; 0.001).This is confirmed in vivo,  BT474GREM1 mice grew significantly larger mammary tumours(p&lt;0.05) and had more PETCT metastatic hotspots. Conclusion Gremlin-1 is correlated with poor outcomes in HER2 patients and promotes breast cancer cellular growth, migration and metastasis.Gremlin-1 is a novel area of research with potential as a prognostic biomarker and therapeutic target for personalised, effective, breast cancer outcomes. Take-home message BMP antagonists are gaining interest for their potential in breast cancer prognosis and therapeutics.This novel area of research shows BMP antagonist Gremlin-1 is of importance in HER2 positive breast cancers. DRAGONS DEN

scholarly journals Fat Composition Measured by Proton Spectroscopy: A Breast Cancer Tumor Marker?

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 564
Author(s):  
Almir Bitencourt ◽  
Varadan Sevilimedu ◽  
Elizabeth A. Morris ◽  
Katja Pinker ◽  
Sunitha B. Thakur
Keyword(s):  
Breast Cancer ◽  
Saturation Index ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Resonance Spectroscopy ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Tumor Tissues ◽  
Cancer Tumor ◽  
Fat Composition

Altered metabolism including lipids is an emerging hallmark of breast cancer. The purpose of this study was to investigate if breast cancers exhibit different magnetic resonance spectroscopy (MRS)-based lipid composition than normal fibroglandular tissue (FGT). MRS spectra, using the stimulated echo acquisition mode sequence, were collected with a 3T scanner from patients with suspicious lesions and contralateral normal tissue. Fat peaks at 1.3 + 1.6 ppm (L13 + L16), 2.1 + 2.3 ppm (L21 + L23), 2.8 ppm (L28), 4.1 + 4.3 ppm (L41 + L43), and 5.2 + 5.3 ppm (L52 + L53) were quantified using LCModel software. The saturation index (SI), number of double bods (NBD), mono and polyunsaturated fatty acids (MUFA and PUFA), and mean chain length (MCL) were also computed. Results showed that mean concentrations of all lipid metabolites and PUFA were significantly lower in tumors compared with that of normal FGT (p ≤ 0.002 and 0.04, respectively). The measure best separating normal and tumor tissues after adjusting with multivariable analysis was L21 + L23, which yielded an area under the curve of 0.87 (95% CI: 0.75–0.98). Similar results were obtained between HER2 positive versus HER2 negative tumors. Hence, MRS-based lipid measurements may serve as independent variables in a multivariate approach to increase the specificity of breast cancer characterization.

The Pattern of Proline, Glutamic Acid, and Leucine-Rich Protein 1 Expression in Chinese Women with Primary Breast Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Primary Breast Cancer ◽  
Chinese Women ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Her 2

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

scholarly journals Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2966-2973 ◽  
Author(s):  
Marco Colleoni ◽  
Bernard F. Cole ◽  
Giuseppe Viale ◽  
Meredith M. Regan ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Triple Negative ◽  
Alkylating Agents ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Tumor Subtypes ◽  
Node Negative Breast Cancer

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

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