scholarly journals Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Tianyi Cheng ◽  
Peiying Chen ◽  
Jingyi Chen ◽  
Yingtong Deng ◽  
Chen Huang
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Matrix Metalloproteinases ◽  
Prognostic Markers ◽  
Immune Functions ◽  
Serine Hydrolase ◽  
Hormone Synthesis ◽  
Secretion Pathway ◽  
Kaplan Meier ◽  
Tumorigenesis And Progression

Breast cancer (BRCA) is the most common cancer in the world, of which incidence rate and mortality are the highest in women. Being responsible for the remodeling and degradation of extracellular matrix proteins, matrix metalloproteinases (MMPs) have been regarded as one of the most important protease family related to tumorigenesis. It has been demonstrated that MMPs play crucial roles in some tumor invasion and metastasis. However, the potential roles of MMPs in tumorigenesis and progression of BRCA and its subtype remain elusive. Herein, we conducted a systematic study on MMPs via a series of database-based retrospective analysis, including TCGA, R Studio, GEPIA, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA and TIMER. As a result, many MMP family members were differentially expressed in patients with BRCA, e.g., the expressions of MMP1, MMP9, MMP11 and MMP13 were up-regulated, whereas the expression levels of MMP19 and MMP28 were down-regulated. MMP9, MMP12, MMP15 and MMP27 were significantly correlated with the clinical stages of BRCA, implying their important roles in the occurrence and development of BRCA. In addition, the survival analysis indicated that different expression pattern of MMPs exhibited distinct outcomes in patient with BRCA, e.g., patients with high expression of MMP2, MMP8, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26 and MMP27 had a prolonged survival time, while the others (MMP1, MMP7, MMP9, MMP12 and MMP15) exhibited poor prognosis. Subsequent functional and network analysis revealed MMPs were mainly correlated with parathyroid hormone synthesis and secretion pathway, collagen metabolism, and their effect on the activities of serine hydrolase, serine peptidase and aminopeptidase. Notably, our analysis showed that the expression of MMPs was significantly correlated with the infiltration of various immune cells in BRCA, including CD8+T cells, CD4+T cells, macrophages, neutrophils, B cells, and dendritic cells, suggesting the close correlations between MMPs and immune functions. In short, our study disclosed MMPs play multiple biological roles in the development of BRCA, MMP1 and MMP9 might be used as independent prognostic markers and potential therapeutic targets for diagnosis and treatment for patients with BRCA.

Co‑expression Network Analysis by WGCNA and Identify Potential Prognostic Markers Associated with Lung Metastasis in Breast Cancer

2021 ◽  
Author(s):  
xixun zhang
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Lung Metastasis ◽  
Prognostic Markers ◽  
Clinical Information ◽  
Preventive Treatment ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Kaplan Meier

Abstract Backgroud: Breast cancer (BC) is an aggressive cancer with a high percentage recurrence and metastasis. As one of the most common distant metastasis organ in breast cancer, lung metastasis has a worse prognosis than that of liver and bone. Therefore, it’s important to explore some potential prognostic markers associated with the lung metastasis in breast cancer for preventive treatment. Methods: In our study, transcriptomic data and clinical information of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules was built by Weighted gene co-expression network analysis (WGCNA) to find out the royalbule modules which is significantly associated with lung metastasis in breast cancer. Then, co-expression genes were analyzed for functional enrichment. Furthermore, the prognostic value of these genes was assessed by GEPIA Database and Kaplan-Meier Plotter. Results: Results showed that the hub genes, LMNB and CDC20, were up-regulated in breast cancer and indicated worse survival. Therefore, we speculate that these two genes play crucial roles in the process of lung metastasis in breast cancer, and can be used as potential prognostic markers in lung metastasis of breast cancer. Conclusion: Collectively, our study identified two potential key genes in the lung metastasis of breast cancer, which might be applied as the prognostic markers of the precise treatment in breast cancer with lung metastasis.

scholarly journals ceRNA Network Development and Tumour-infiltrating Immune Cell Analysis in Metastatic Breast Cancer of Bone

2020 ◽  
Author(s):  
Shuzhong Liu ◽  
An Song ◽  
Xi Zhou ◽  
Zhen Huo ◽  
Siyuan Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Bone Metastasis ◽  
Immune Cell ◽  
Rna Expression ◽  
Cell Analysis ◽  
Breast Cancer Patients ◽  
Cerna Network ◽  
Follicular Helper ◽  
Kaplan Meier

Abstract Background: Advanced breast cancer commonly metastasises to the bone and the molecular mechanism explaining the bone affinity of breast cancer cells is unclear. Thus, we developed nomograms based on a competing endogenous RNA (ceRNA) network and analysed tumour-infiltrating immunecells to elucidate the molecular pathways that may predict the prognosis of breast cancer patients.Methods: We obtained the RNA expression profile of 1091 primary breast cancer samples from The Cancer Genome Atlas database, 58 of which had bone metastasis. We analysed differential RNA expression patterns between breast cancer with and without bone metastasis and developed a ceRNA network. Cibersort was employed to differentiate between immune cell types based on tumour transcripts. Nomograms were then established using the ceRNA network and immune cell analysis. The value of prognostic factors was evaluated by Kaplan-Meier survival analysis and Cox proportional risk model.Results: There were significant differences in lncRNAs, 18 miRNAs, and 20mRNAs between breast cancer with and without bone metastasis, which were used to construct a ceRNA network. We found that the protein-coding genes gjb3, cammv, ptprz1,and fbn3 were significant in our Kaplan-Meier analysis. We also observed significant differences in plasma cell and follicular helper T cell populations between the two groups. In addition, the proportions of mast cells, gamma delta T cells, and plasma cells differed depending on disease location and stage. Our analysis revealed that a high proportion of follicular helper T cells and a low proportion of eosinophils promoted survival and that dlx6-as1, wnt6,and gabbr2expression may be related to bone metastasis of breast cancer.Conclusions: We provided a bioinformatic basis for exploring the molecular mechanism of bone metastasis in breast cancer patients and identified factors that may predict this.

scholarly journals Identification of Prognostic Biomarkers Among DAAM1, FHOD1,FMN2 and INF2 in Breast Cancer Patients

2021 ◽  
Author(s):  
Yin-Hai Dai ◽  
Fuping Li ◽  
Wei-Jie Kong ◽  
Xue-Qin Zhang ◽  
Mao Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Survival Data ◽  
Mrna Level ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Migration Of Cells ◽  
Kaplan Meier Plotter

Abstract Background:The formin family proteins are main regulators of actin filaments, which play a crucial role in the migration of cells and carcinogenesis.The specific functions of the formin family proteins in breast cancer still remain unknown.To dissolve this problem,we selected four formin proteins including DAAM1,FHOD1, FMN2 and INF2 and investigated their mRNA expression and survival data in BC(breast carcinoma) patients using diverse databases.Methods:we used these databases including Oncomine, Ualcan, GEPIA 2,HumanProtein Atlas,Metascape,Kaplan-Meier plotter,cBioPortal and TIMER and the software of Cytoscape in our study.Results:DAAM1 and FMN2 were lowly expressed in BC tissues,while FHOD1 and INF2 were highly expressed in BC tissues.The expression levels of DAAM1, FMN2 and FHOD1 were relevant to major subclasses,and the mRNA level of FHOD1 was related to cancer staging.Moreover,High mRNA levels of FHOD1 and INF2 were relevant to poorer prognosis of BC patients,while low mRNA level of DAAM1 was correlated with better prognosis.we also found that there were significant associations between the expressions of DAAM1,FHOD1,FMN2 and INF2 and six types of infiltrated immune cells(B Cells,CD4+T cells,CD8+T cells, neutrophil,macrophage,and dendritic cell).Conclusions:our study indicated that FHOD1 and INF2 were potential biomarkers to identify short survival of BC patients,FMN2 was potential prognostic marker to suggest favorable survival of BC patients.

scholarly journals CENPL, ISG20L2, LSM4 , MRPL3 Are Four Novel Hub Genes and May Serve as Diagnostic and Prognostic Markers in Breast Cancer

2021 ◽  
Author(s):  
Jinbao Yin ◽  
Chen Lin ◽  
Meng Jiang ◽  
Xinbin Tang ◽  
Danlin Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Prognostic Markers ◽  
Hub Genes ◽  
Kaplan Meier ◽  
Detection Technology ◽  
Prevalent Disease ◽  
Depth Study ◽  
Functional Mechanisms

Abstract As a highly prevalent disease among women worldwide, breast cancer remains in urgent need of further elucidation its molecular mechanisms to improve the patient outcomes. Identifying hub genes involved in the pathogenesis and progression of breast cancer can potentially help to unveil mechanism and also provide novel diagnostic and prognostic markers. In this study, we integrated multiple bioinformatic methods and RNA in situ detection technology to identify and validate hub genes. EZH2 was recognized as a key gene by PPI network analysis. CENPL, ISG20L2, LSM4, MRPL3 were identified as four novel hub genes through the WGCNA analysis and literate search. Among these, many studies on EZH2 in breast cancer have been reported, but no studies are related to the roles of CENPL, ISG20L2, MRPL3 and LSM4 in breast cancer. These four novel hub genes were up-regulated in tumor tissues and associated with cancer progression. The receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis indicated that these four hub genes are promising candidate genes that can serve as diagnostic and prognostic biomarkers for breast cancer. Moreover, these four newly identified hub genes as aberrant molecules in the maintenance of breast cancer development, their exact functional mechanisms deserve further in-depth study.

Bioinformatics analysis of immune infiltration patterns in breast cancer for identification of prognostic markers

2019 ◽  
Author(s):  
Yan Yao ◽  
Tingting Zhang ◽  
Lingyu Qi ◽  
Ruijuan Liu ◽  
Gongxi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Prognostic Markers ◽  
T Cell Subsets ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Significant Difference

Abstract Background/purpose Cancer immunotherapy has revolutionized the clinical treatment of several tumors. Immune infiltration has been found to be closely related to clinical prognosis, but it shows limited activity in breast cancer (BC). Therefore, this study aimed to explore the infiltration pattern of immune cells in BC, and to find potential prognostic markers and new therapeutic targets.Patients and methods We downloaded the immune genome data of BC from the Cancer Genome Atlas (TCGA), and analyzed the tumor- infiltrating immune cells (TIICs) in BC for the first time using the CIBERSORT algorithm. The aim of this study was to assess the proportions of 22 immune cell subsets in BC and examine the correlation between each TIIC and overall survival (OS) as well as clinical characteristics.Results The results indicated that: (1) there was a significant difference between the immune infiltration spectrum of cancerous and adjacent tissues, with M2 macrophages, M0 macrophages, and CD4 + T cells being highly expressed in BC; (2) CD8 + T cells were positively correlated with activated CD4 + memory T cells and negatively correlated with M0 macrophages, and M2 macrophages was inversely correlated with M1 macrophages, T cells regulatory, T cells CD8; (3) T cells, macrophages and BC TNM stage, age, clinical stage were correlated (P < 0.05); and (4) high expression of M2 macrophage markers could be an independent biomarker of poor prognosis and a potential therapeutic target for BC.Conclusion This study provides a new research method for the systematic study of immune cells in the BC tumor microenvironment, and provides theoretical guidance for further experiments to verify M2 macrophages and T cell subsets as a potential target for immunotherapy and prognosis.

scholarly journals The Emerging Role of MicroRNAs in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Zhiguang Yang ◽  
Zhaoyu Liu
Keyword(s):  
Breast Cancer ◽  
Prognostic Markers ◽  
Recent Literature ◽  
New Drugs ◽  
Effective Management ◽  
Therapeutic Outcomes ◽  
Tumorigenesis And Progression ◽  
New Biomarkers ◽  
Common Malignancy

Breast cancer (BC) is the most common malignancy in women. Due to BC heterogeneity, complexity, and metastasis, many BC patients do not successfully respond to therapies. The effective management of BC depends on early diagnosis and monitoring of drug response. Therefore, identifying new biomarkers for the diagnosis, prognosis, and development of new drugs is urgently required. Dysregulation of microRNAs (miRNAs) participates in the tumorigenesis and progression of cancers, especially breast cancer (BC). Several studies demonstrated that miRNAs could perform their function as oncogenes or tumor suppressors. This review describes recent progress on the role of microRNAs in the diagnosis, prognosis, hallmark, and treatment of BC. According to a recent literature survey, miRNAs play a pivotal role in the regulation of hallmarks of cancer, such as proliferation, apoptosis, invasion, metastasis, and tumor stemness. Many miRNAs are potential biomarkers for BC for diagnosis, and some are indicators of prognosis. Moreover, circulating miRNA profiles, as minimally invasive, diagnostic, and prognostic markers, are broadly used in BC therapy, and some miRNAs are good predictors of therapeutic outcomes. Other miRNAs are involved in overcoming chemoresistance and in increasing BC drug sensitivity.

scholarly journals CENPL, ISG20L2, LSM4, MRPL3 are four novel hub genes and may serve as diagnostic and prognostic markers in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinbao Yin ◽  
Chen Lin ◽  
Meng Jiang ◽  
Xinbin Tang ◽  
Danlin Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Prognostic Markers ◽  
Characteristic Analysis ◽  
Hub Genes ◽  
Kaplan Meier ◽  
Detection Technology ◽  
Prevalent Disease ◽  
Depth Study

AbstractAs a highly prevalent disease among women worldwide, breast cancer remains in urgent need of further elucidation its molecular mechanisms to improve the patient outcomes. Identifying hub genes involved in the pathogenesis and progression of breast cancer can potentially help to unveil mechanism and also provide novel diagnostic and prognostic markers. In this study, we integrated multiple bioinformatic methods and RNA in situ detection technology to identify and validate hub genes. EZH2 was recognized as a key gene by PPI network analysis. CENPL, ISG20L2, LSM4, MRPL3 were identified as four novel hub genes through the WGCNA analysis and literate search. Among these, many studies on EZH2 in breast cancer have been reported, but no studies are related to the roles of CENPL, ISG20L2, MRPL3 and LSM4 in breast cancer. These four novel hub genes were up-regulated in tumor tissues and associated with cancer progression. The receiver operating characteristic analysis and Kaplan–Meier survival analysis indicated that these four hub genes are promising candidate genes that can serve as diagnostic and prognostic biomarkers for breast cancer. Moreover, these four newly identified hub genes as aberrant molecules in the maintenance of breast cancer development, their exact functional mechanisms deserve further in-depth study.

scholarly journals PECAM-1 is a prognostic-related biomarker and correlated with immune infiltrates in breast cancer

2021 ◽  
Author(s):  
Qingfang Yue ◽  
Fei Wang ◽  
Fei Cao ◽  
Xianglong Duan ◽  
Jun Bai
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Invasive Carcinoma ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Immune Gene ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Background: Breast invasive carcinoma (BRCA) is the primary cause of cancer-associated mortality worldwide. Platelet endothelial cell adhesion molecule 1 (PECAM-1) has been implicated in a number of important biological processes. However, the interrelation between PECAM-1 gene expression, tumor immunity, and prognosis of patients with BRCA is unclear. The current study is aimed to analyze the expression and clinical significance of PECAM-1 in breast cancer and the correlation between PECAM-1 and immune infiltrations. Methods: The differential expressions of PECAM-1 in breast cancer tissues and normal tissues were evaluated via exploring TIMER, Oncomine and UALCAN databases; the relationship within expression level of PECAM-1 and outcome of breast patients was evaluated via Kaplan-Meier plotter and PrognoScan; the methylation of PECAM-1 were investigated through the MethSurv platform; the correlation between PECAM-1 and tumor immune cell infiltration was further investigated by TIMER and GEPIA databases; the correlation between PECAM-1 and gene makers of immune infiltration were checked using TIMER and GEPIA. Results: There were significant differences in PECAM-1 expression levels between breast invasive carcinoma tissues and adjacent normal tissues. Low PECAM-1 expression was significantly related to poor overall survival, progression-free survival and distant metastasis free survival in patients with breast cancer. In DNA methylation level, PECAM-1 hypermethylation in three CpG sites (cg20830094, cg00427260 and cg00879592) showed poor survival in breast cancer. PECAM-1 expression exhibited significantly positive correlations with the levels of infiltrated B cell, CD4+T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in breast cancer. Furthermore, PECAM-1 expression is positively correlated with multiple immune gene makers in breast cancer.Conclusion: The expression of PECAM-1 can serves as a prognostic biomarker in breast invasive carcinoma and is correlated with immune infiltrates.

scholarly journals Transcriptional Expressions of CXCL9/10/12/13 as Prognosis Factors in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yan Li ◽  
Mingqiang Liang ◽  
Yuxiang Lin ◽  
Jinxing Lv ◽  
Minyan Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Predictive Biomarkers ◽  
Nodal Metastasis ◽  
Transcriptional Level ◽  
Breast Cancer Patients ◽  
Oncomine Database ◽  
Kaplan Meier ◽  
The Impact

CXCLs play critical roles in antitumor immunity by activating tumor-specific immune responses and stimulating tumor proliferation, thus affecting patient outcomes. However, the expression and prognostic values of CXCLs in breast cancer have not been well clarified. The aim of this study was to investigate the impact of CXCLs transcriptional expression on breast cancer patients. Oncomine database, GEPIA (Gene Expression Profiling Interactive Analysis), UALCAN, Kaplan–Meier Plotter, TIMER (Tumor Immune Estimation Resource), and DAVID were used in our study. The transcriptional levels of CXCL9/10/11/13 in breast cancer tissues were significantly elevated while the transcriptional levels of CXCL1/2/3/12 were decreased based on intersections of Oncomine database and GEPIA. Among them, breast cancer patients with high transcriptional levels of CXCL2/9/10/12/13 and low transcriptional level of CXCL3 were associated with a better prognosis. We also found that most of CXCLs expressions are significantly correlated with known prognostic factors, such as patient’s age, major subclasses, individual cancer stages, and nodal metastasis status. In addition, the expression of CXCL9/10/12/13 was also indicated to be correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). The functions of differentially expressed CXCLs are primarily related to the immune response and cytokine-cytokine receptor interactions. Our results may provide novel evidence of new prognostic or predictive biomarkers for breast cancer patients.

Identification of potential prognostic markers associated with lung metastasis in breast cancer by coexpression network analysis

2021 ◽  
pp. 1-12
Author(s):  
Xixun Zhang
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Lung Metastasis ◽  
Prognostic Markers ◽  
Clinical Information ◽  
Preventive Treatment ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Breast cancer (BC) is an aggressive cancer with a high percentage recurrence and metastasis. As one of the most common distant metastasis organ in BC, lung metastasis has a worse prognosis than that of liver and bone. Therefore, it’s important to explore some potential prognostic markers associated with the lung metastasis in BC for preventive treatment. In this study, transcriptomic data and clinical information of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Co-expression modules constructed by weighted gene co-expression network analysis (WGCNA) found the royal blue module was significantly associated with lung metastasis in BC. Then, co-expression genes of this module were analyzed for functional enrichment. Furthermore, the prognostic value of these genes was assessed by GEPIA Database and Kaplan-Meier Plotter. Results showed that the hub genes, LMNB and CDC20, were up-regulated in BC and had a worse survival of the patients. Therefore, we speculate that these two genes play crucial roles in the process of lung metastasis in BC, which can be used as potential prognostic markers in lung metastasis of BC. Collectively, our study identified two potential key genes in the lung metastasis of BC, which might be applied as the prognostic markers of the precise treatment in breast cancer with lung metastasis.

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