scholarly journals Systemic Multi-Omics Analysis Reveals Amplified P4HA1 Gene Associated With Prognostic and Hypoxic Regulation in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Manikandan Murugesan ◽  
Kumpati Premkumar
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Hypoxic Condition ◽  
Distant Metastases ◽  
Time Intervals ◽  
Free Survival ◽  
Protein Protein Interaction ◽  
Stage 1 ◽  
Insight Into ◽  
Geo Database

Breast cancer (BC) is a common malignant tumor in females around the world. While multimodality therapies exist, the mortality rate remains high. The hypoxic condition was one of the potent determinants in BC progression. The molecular mechanisms underpinning hypoxia and their association with BC can contribute to a better understanding of tailored therapies. In this study, two hypoxic induced BC transcriptomic cohorts (GSE27813 and GSE47533) were assessed from the GEO database. The P4HA1 gene was identified as a putative candidate and significantly regulated in hypoxic BC cells compared to normal BC cells at different time intervals (6 h, 9 h, 16 h, 32 h, and 48 h). In patients with Luminal (p < 1E-12), triple-negative subclasses (p = 1.35059E-10), Stage 1 (p = 8.8817E-16), lymph node N1 (p = 1.62436E-12), and in the 40–80 age group (p = 1.62447E-12), the expression of P4HA1 was closely associated with the clinical subtypes of BC. Furthermore, at the 10q22.1 chromosomal band, the P4HA1 gene displayed a high copy number elevation and was associated with a poor clinical regimen with overall survival, relapse-free survival, and distant metastases-free survival in BC patients. In addition, using BioGRID, the protein–protein interaction (PPI) network was built and the cellular metabolic processes, and hedgehog pathways are functionally enriched with GO and KEGG terms. This tentative result provides insight into the molecular function of the P4HA1 gene, which is likely to promote hypoxic-mediated carcinogenesis, which may favor early detection of BC and therapeutic stratification.

Insight into p95HER2 in Breast Cancer: Molecular Mechanisms and Targeted Therapies

2012 ◽  
Vol 6 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Ramon Andrade de Mello ◽  
Alessandro de Vasconcelos ◽  
Ronaldo A Ribeiro ◽  
Ines Pousa ◽  
Noemia Afonso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Insight Into

scholarly journals Downregulated ZNF132 Predicts Unfavorable Outcomes in Breast Cancer via Hypermethylation Modification

2019 ◽  
Author(s):  
Zhao Liu ◽  
Jiaxin Liu ◽  
Man Xue ◽  
Weifan Zhang ◽  
Xinhui Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Prognostic Significance ◽  
Suppressor Gene ◽  
Clinical Samples ◽  
Free Survival ◽  
Normal Tissues ◽  
Bioinformatic Tools ◽  
Its Gene ◽  
The Status

Abstract Background: Methylation modification of tumor suppressor gene is one of the most critical mechanisms in human breast cancer (BC). Some biomarkers, including HER2, ER and PR, have been used in clinical practice, however, the effective was limited in terms of high recurrence and mortality rate. Thus, a better diagnostic and therapeutic target for BC is urgent. To date, no study provide information on the status of ZNF132 in BC or analyze diagnosis and prognostic significance of ZNF132 in BC. Methods: In the present study, we investigated the expression and clinical signifcance of ZNF132 by TCGA database and clinical samples analysis. Besides, a further exploration was performed to assess the molecular mechanisms of ZNF132 using the multiple bioinformatic tools. Importantly, a MSP assay was executed to confirm the epigenetic alteration of ZNF132. Results: Our results showed that the mRNA expression of ZNF132 was significantly downregulated in BC tissues, the consistent results was obtained by immunohistochemistry assessment. Importantly, survial analysis revealed that the lower expression of ZNF132 was remarkably correlated to Relapse Free Survival (RFS), but not Overall Survival (OS). Besides, the ROC curve confirmed ZNF132 had powerful sensitivity and specificity to distinguish between BC and adjacent normal tissues. Finally, MSP analysis demonstrated that ZNF132 was hypermethylated in BC tissues. Interestingly, ZNF132 methylation level was negatively correlated with its gene expression. Conclusions: Our results revealed that hypermethylation of ZNF132 contributed to its downregulated expression and could be identified as a new diagnostic and prognostic marker in BC.

Pattern of care and survival in older women with breast cancer in India

2010 ◽  
Vol 9 (4) ◽  
pp. 237-245 ◽  
Author(s):  
Budhi S. Yadav ◽  
Suresh C. Sharma ◽  
G. Menu ◽  
A. Mohmad ◽  
Firuza D. Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormonal Therapy ◽  
Elderly Women ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Therapy Outcomes ◽  
Pattern Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Study Population

AbstractPurpose: To determine the pattern of care and survival in older patients with breast cancer.Methods: The study population included 228 women aged ≥60 years with breast cancer treated between 1992 and 2002. Analysis was done for surgery, radiotherapy (RT), chemotherapy and hormonal therapy. Outcomes studied were locoregional recurrence (LRR) distant metastases, disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. Kaplan–Meier method was used to estimate DFS and OS.Results: Mastectomy was done in 208 (91%) patients and conservative breast surgery (CBS) only in 20 (9%) patients. Majority of the patients received adjuvant RT 179 (78.5%). Chemotherapy was given to 49 (21.5%) patients and hormones to 204 (89.5%) patients. LRR with or without distant metastases was 7% and distant metastasis rate was 19.3%. DFS at 10 years was 69%. With RT, DFS was 76% in patients aged <65 years and 73% in aged ≥65 years (p = 0.13). It was 73 and 86%, respectively, with chemotherapy (p = 0.041). DFS with hormones was 96% in patients aged ≥65 years and 79% in aged <65 years (p = 0.028). The OS was 74% at 10 years. RT improved OS in all patients. OS with chemotherapy was 94% in patients ≥65 years, and 82% in patients <65 years (p = 0.044). With hormonal therapy OS was 96% in patients aged ≥65 years and 78% in patients <65 years (p = 0.020).Conclusion: CBS rate and chemotherapy use is very low in elderly women with breast cancer in India. Adjuvant RT, chemotherapy and hormonal therapy offered a therapeutic advantage in these patients.

scholarly journals Guideline-concordant chemotherapy in patients with hormone receptor-positive and node-positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients

2019 ◽  
Vol 301 (2) ◽  
pp. 573-583
Author(s):  
Clara Taubenhansl ◽  
Olaf Ortmann ◽  
Michael Gerken ◽  
Elisabeth C. Inwald ◽  
Monika Klinkhammer-Schalke
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Hormone Receptor ◽  
Cox Regression ◽  
Distant Metastases ◽  
Free Survival ◽  
Node Positive ◽  
Hormone Receptor Positive ◽  
Kaplan Meier ◽  
Multivariable Analyses

Abstract Purpose The German guideline for breast cancer recommends using chemotherapy (CHT) in patients with hormone receptor-positive and node-positive, invasive breast cancer. The aim of this study was to analyse the effects of CHT in this patient group on overall survival (OS) and distant metastases-free survival (DMFS), especially considering the 70-year threshold. Methods 1772 patients from the clinical cancer registry Regensburg (Germany) with hormone receptor-positive and node-positive, invasive breast cancer diagnosed between 2003 and 2013 were analysed in a retrospective cohort study. OS and DMFS were evaluated by means of Kaplan–Meier and multivariable Cox-regression method. Results were further examined according to age at diagnosis. Results The comparison of 1544 patients with CHT to 228 patients without CHT showed a significant benefit for CHT regarding 5-year OS (91.3% vs. 76.8%) and 5-year DMFS (86.7% vs. 74.4%, both p < 0.001). Likewise, better OS and DMFS were seen in patients aged < 70 years using CHT compared to patients without CHT of the same age. Patients aged ≥ 70 years with CHT had a minimal benefit regarding 5-year OS compared to patients without CHT, but no advantage considering DMFS. All results were confirmed in multivariable analyses except for patients being ≥ 70 years of age. Conclusion Patients with hormone receptor-positive and node-positive, invasive breast cancer benefit from chemotherapy with regard to a significantly better overall and distant metastases-free survival, although chemotherapy use in patients aged ≥ 70 years results in a smaller benefit considering OS and no benefit considering DMFS.

scholarly journals Time to Start Adjuvant Systemic Treatment in Breast Cancer; a Retrospective Cohort Study

2017 ◽  
Vol 6 (2) ◽  
pp. 60
Author(s):  
Amal Rayan ◽  
Hosam A. Hasan
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Systemic Treatment ◽  
University Hospital ◽  
World Health ◽  
Optimal Time ◽  
Time Intervals ◽  
Free Survival ◽  
Adjuvant Systemic Treatment ◽  
The Impact

Background: According to the World Health Organization (WHO), early diagnosis of cancer was associated with increasing rates of survival for cancers as breast, cervix, mouth, larynx, colon, rectum and skin. Still the optimal time to start adjuvant treatment after definitive surgery is uncertainAim of study: to evaluate the impact of delay to start adjuvant treatment in different biologic subtypes of breast cancer on treatment outcomes as regard response, failure free survival (FFS).Patients and methods: It involved 107 patients with nonmetastatic breast cancer presented to clinical oncology department, Assiut university hospital from January 2011 to December 2012, and were eligible for adjuvant systemic treatment, The time from surgery to the start of 1st cycle of adjuvant systemic treatment was calculated, then this time was divided into three time intervals; ≤30 days, >30 - ≤60 days, and >60 days.Results: 41.1%, 45.8%, 13.1% of patients received adjuvant treatment within 30 days, <30-60 days, and more than 60 days respectively, the median failure free survival was 50±2.104 months (95% CI=45.877-54.125) and was significantly decreased with increasing the time but not significantly differed between different time intervals in the whole study patients, nor in different biologic subtypes except luminal B, patients started early adjuvant treatment, relapsed late with significant effect of different time intervals on the time to relapse, local and distant relapses (P<0.000, P<0.001, P<0.02).Conclusion: Adjuvant systemic treatment for breast cancer should be initiated as early as possible better within 30 days of surgery because of significant poor effect of delay to initiate adjuvant treatment on FFS and TTR.

The biology of neoadjuvant chemotherapy for breast cancer.

2002 ◽  
pp. 183-195 ◽  
Author(s):  
S Cleator ◽  
M Parton ◽  
M Dowsett
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumour Response ◽  
Disease Free Survival ◽  
Biological Information ◽  
Free Survival ◽  
Pathological Complete Remission ◽  
Chemotherapeutic Response ◽  
Disease Free ◽  
Insight Into

Neoadjuvant/pre-surgical medical therapy of breast cancer provides a unique opportunity to derive biological information related to tumour response. Large clinical trials of neoadjuvant chemotherapy have established that pathological complete remission is an independent predictor of improved disease-free survival. Clinical response has been found to parallel substantial reductions in the proliferation of breast cancer cells. Increased apoptosis also occurs, but it is not closely associated with response. Numerous biological markers such as p53, bcl-2, oestrogen receptor (ER) and HER2 have been assessed for their possible role in chemoresistance/response, but the data are not clear at this stage. Continuing work using cDNA microarrays may yield new, more reliable indices of likely response and an improved insight into biological processes related to chemotherapeutic response.

scholarly journals FRI0584 SCREENING AND IDENTIFICATION OF BIOMARKERS IN MYOSITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 896-897
Author(s):  
W. Liu ◽  
X. Zhang
Keyword(s):  
Gene Expression ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network ◽  
Geo Database

Background:Myositis, including dermatomyositis and polymyositis, is autoimmune disorders that is characterized by muscle degeneration in the proximal extremities, with the complications of weakness of muscles, interstitial lung disease and vascular lesions, even leading to death in an acute progressive process[1,2]. However, the molecular mechanisms of myositis are rarely understood.Objectives:Identify the candidate genes in myositis.Methods:Microarray datasets GSE128470, GSE48280 and GSE39454 were extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and function enrichment analyses were conducted. The protein-protein interaction network and the analyses of hub genes were performed with STRING and Cytoscape.Results:There were 98 DEGs, of which the function and pathways enrichment analyses showed defense response, immune response, response to virus, inflammatory response, response to wounding, cell adhesion, cell proliferation, cell death and macromolecule metabolic process. 20 hub genes were identified, of which 7 including IRF9 TRIM22 MX2 IFITM1 IFI6 IFI44 IFI44L had not been reported in the literature, related to the response to virus, immune response, transcription from RNA polymerase II promoter, cell apoptosis, cell death. The verification analysis about the 7 genes in GSE128314 showed significant differences in myositis.Conclusion:In conclusion, DEGs and hub genes identified in our study showed the potential molecular mechanisms in myositis, providing the helpful targets for diagnosis and clinical strategy of myositis.References:[1] Wu H, Geng D, Xu J. An approach to the development of interstitial lung disease in dermatomyositis: a study of 230 cases in China[J]. Journal of International Medical Research. 2013;41(2):493–501.[2] Fathi M, Dastmalchi M, Rasmussen E, Lundberg IE, Tornling G. Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis[J]. Annals of the Rheumatic Diseases. 2004;63(3):297–301.Figure 1.The protein-protein interaction network of 20 hub genesFigure 2.7 genes in GSE128314 showed significant differences in myositisAcknowledgments:The authors acknowledge the efforts of the Gene Expression Omnibus (GEO) database. The interpretation and reporting of these data are the sole responsibility of the authors.Disclosure of Interests:None declared

scholarly journals Molecular Mechanisms of Trastuzumab-Based Treatment in HER2-Overexpressing Breast Cancer

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Rita Nahta
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Trastuzumab Resistance ◽  
Surface Receptors ◽  
Downstream Signaling ◽  
The Past ◽  
Her2 Signaling ◽  
Insight Into ◽  
Induce Antibody

The past decade of research into HER2-overexpressing breast cancer has provided significant insight into the mechanisms by which HER2 signaling drives tumor progression, as well as potential mechanisms by which cancer cells escape the anticancer activity of HER2-targeted therapy. Many of these preclinical findings have been translated into clinical development, resulting in novel combinations of HER2-targeted therapies and combinations of trastuzumab plus inhibitors of resistance pathways. In this paper, we will discuss proposed mechanisms of trastuzumab resistance, including epitope masking, cross signaling from other cell surface receptors, hyperactive downstream signaling, and failure to induce antibody-dependent cellular cytotoxicity. In addition, we will discuss the molecular mechanisms of action of dual HER2 inhibition, specifically the combination of trastuzumab plus lapatinib or trastuzumab with pertuzumab. We will also discuss data supporting therapeutic combinations of trastuzumab with agents targeted against molecules implicated in trastuzumab resistance. The roles of insulin-like growth factor-I receptor and the estrogen receptor are discussed in the context of resistance to HER2-targeted therapies. Finally, we will examine the major issues that need to be addressed in order to translate these combinations from the bench to the clinic, including the need to establish relevant biomarkers to select for those patients who are most likely to benefit from a particular drug combination.

scholarly journals Identification of potential genes related to breast cancer brain metastasis in breast cancer patients

2021 ◽  
Author(s):  
Lijian Zhang ◽  
Luxuan Wang ◽  
Hua Yang ◽  
Chunhui Li ◽  
Chuan Fang
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Geo Database

Brain metastases (BM) usually develop in breast cancer patients. Thus, the molecular mechanisms of breast cancer brain metastasis (BCBM) are of great importance in designing therapeutic strategies to treat or prevent BCBM. This study attempted to identify novel diagnostic and prognostic biomarkers of BCBM. Two datasets (GSE125989 and GSE100534) were obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) in cases of breast cancer with and without brain metastasis. A total of 146 overlapping DEGs, including 103 up-regulated genes and 43 down-regulated genes, were identified. Functional enrichment analysis showed that these DEGs were mainly enriched for functions including extracellular matrix organization and collagen catabolic fibril organization. Using protein-protein interaction (PPI) and principal component analysis (PCA) analysis, we identified 10 key genes, including LAMA4, COL1A1, COL5A2, COL3A1, COL4A1, COL5A1, COL5A3, COL6A3, COL6A2, and COL6A1. Additionally, COL5A1, COL4A1, COL1A1, COL6A1, COL6A2 and COL6A3 were significantly associated with the overall survival of BC patients. Furthermore, COL6A3, COL5A1, and COL4A1 were potentially correlated with BCBM in human epidermal growth factor 2 (HER2) expression. Additionally, the miR-29 family might participate in the process of metastasis by modulating the cancer microenvironment. Based on datasets in the GEO database, several DEGs have been identified as playing potentially important roles in BCBM in BC patients.

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