scholarly journals Prognostic Biomarkers on a Competitive Endogenous RNA Network Reveals Overall Survival in Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenxing Qin ◽  
Feng Qi ◽  
Jia Li ◽  
Ping Li ◽  
Yuan-Sheng Zang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Prognostic Model ◽  
Triple Negative ◽  
Cox Regression ◽  
Critical Role ◽  
Differentially Expressed ◽  
Cerna Network ◽  
Competitive Endogenous Rna

The objective of this study was to construct a competitive endogenous RNA (ceRNA) regulatory network using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with triple-negative breast cancer (TNBC) and to construct a prognostic model for predicting overall survival (OS) in patients with TNBC. Differentially expressed lncRNAs, miRNAs, and mRNAs in TNBC patients from the TCGA and Metabric databases were examined. A prognostic model based on prognostic scores (PSs) was established for predicting OS in TNBC patients, and the performance of the model was assessed by a recipient that operated on a distinctive curve. A total of 874 differentially expressed RNAs (DERs) were screened, among which 6 lncRNAs, 295 miRNAs and 573 mRNAs were utilized to construct targeted and coexpression ceRNA regulatory networks. Eight differentially expressed genes (DEGs) associated with survival prognosis, DBX2, MYH7, TARDBP, POU4F1, ABCB11, LHFPL5, TRHDE and TIMP4, were identified by multivariate Cox regression and then used to establish a prognostic model. Our study shows that the ceRNA network has a critical role in maintaining the aggressiveness of TNBC and provides comprehensive molecular-level insight for predicting individual mortality hazards for TNBC patients. Our data suggest that these prognostic mRNAs from the ceRNA network are promising therapeutic targets for clinical intervention.

scholarly journals TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumour growth and correlates with poor prognosis

2021 ◽  
Author(s):  
Jianyang Hu ◽  
Yuni Lai ◽  
Hao Huang ◽  
Saravanan Ramakrishnan ◽  
Yilin Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Cox Regression ◽  
Critical Role ◽  
Rna Seq ◽  
Data Set ◽  
Super Enhancer

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. By performing multiomic profiling, we recently uncovered super-enhancer heterogeneity between breast cancer subtypes. Our data also revealed TCOF1 as a putative TNBC-specific super-enhancer-regulated gene. TCOF1 plays a critical role in craniofacial development but its function in cancer remains unclear. Methods Overall survival and multivariant Cox regression analyses were conducted using the METABRIC data set. The effect of TCOF1 knockout on TNBC growth and stemness was evaluated by in vitro and in vivo assays. RNA-seq and rescue experiments were performed to explore the underlying mechanisms. Results TCOF1 is frequently upregulated in TNBC and its elevated expression correlates with shorter overall survival. TCOF1 depletion significantly inhibits the growth and stemness of basal-like TNBC, but not of mesenchymal-like cells, highlighting the distinct molecular dependency in different TNBC subgroups. RNA-seq uncovers several stem cell molecules regulated by TCOF1. We further demonstrate that KIT is a downstream effector of TCOF1 in mediating TNBC stemness. TCOF1 expression in TNBC is regulated by the predicted super-enhancer. Conclusions TCOF1 depletion potently attenuates the growth and stemness of basal-like TNBC. Expression of TCOF1 may serve as a TNBC prognostic marker and a therapeutic target.

scholarly journals Differential expression of cyclin A2 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells ◽  
Cyclin A2

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin A2, CCNA2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CCNA2 was also differentially expressed in bulk tumor in human breast cancer (3). CCNA2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CCNA2 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of CCNA2 was correlated with overall survival in patients with basal-like 1, basal-like 2, and mesenchymal subtype disease. CCNA2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

scholarly journals An 8-lncRNA Signature Predicts Survival of Triple-Negative Breast Cancer Patients Without Germline BRCA1/2 Mutation

2020 ◽  
Author(s):  
Minling Liu ◽  
Wei Dai ◽  
Mengyuan Zhu ◽  
Xueying Li ◽  
Shan Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Validation Cohort ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Risk Scores ◽  
Training Cohort

Abstract Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.

scholarly journals Differential expression of cell division cycle-associated 5 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cell Division ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cell division cycle-associated 5, CDCA5, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CDCA5 was also differentially expressed in bulk tumor in human breast cancer (3). CDCA5 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CDCA5 in primary tumors of the breast was correlated with overall survival in patients with luminal A type cancer, while within triple negative breast cancer, primary tumor expression of CDCA5 was correlated with overall survival in patients with mesenchymal subtype disease. CDCA5 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

scholarly journals An 8-lncRNA signature predicts the survival of triple-negative breast cancer patients without germline BRCA1/2 mutation

2021 ◽  
Vol 3 (3) ◽  
pp. 15-32
Author(s):  
Minling LIU ◽  
Wei DAI ◽  
Mengyuan ZHU ◽  
Xueying LI ◽  
Min WEI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Training Cohort ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy

Purpose: TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment. Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort. Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The qPCR assay was performed to confirm the expressions and clinicopathological correlations of two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm. Results: We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. Patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores (P=0.00018 and P =0.0068 respectively). 30 paired specimens of TNBC without gBRCAm in our center showed that two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed, and significantly associated with tumor grade and invasion. Conclusion: We constructed a novel 8-lncRNA signature which significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8 lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targets which function needed further exploration.

scholarly journals Construction and Validation of a Prognostic Risk Model for Triple Negative Breast Cancer Based on Autophagy-Related Genes

2021 ◽  
Author(s):  
Cheng Yan ◽  
Qingling Liu ◽  
Ruoling Jia
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Risk Model ◽  
Cox Regression ◽  
Risk Group ◽  
Lasso Regression ◽  
Cox Regression Analysis

Abstract Background: Autophagy plays an important role in triple negative breast cancer (TNBC). However, the prognostic value of autophagy-related genes (ARGs) in TNBC remains unknown. In this study, we established a survival model to evaluate the prognosis of TNBC patients using ARGs signature.Methods: A total of 222 autophagy-related genes were downloaded from The Human Autophagy Database. The RNA-sequencing data and corresponding clinical data of TNBC were obtained from the TCGA database. Differential gene expression of ARGs (DE-ARGs) between normal samples and TNBC samples was determined by the EdgeR software package. Then, univariate Cox, Lasso, and multivariate Cox regression analyses were performed. According to the Lasso regression results based on univariate Cox, we identified a prognostic signature for overall-survival (OS), which was further validated by using GEO cohort. We also found an independent prognostic marker that can predict the clinicopathological features of TNBC. Furthermore, a nomogram was drawn to predict the survival probability of TNBC patients, which could help in clinical decision for TNBC treatment. Finally, we validated the requirement of a ARG in our model for TNBC cell survival and metastasis.Results: There are 43 differentially expressed ARGs (DE-ARGs) were identified between normal and tumor samples. A risk model for OS using CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74 and VAMP3 by Lasso regression analysis was established based on univariate Cox regression analysis. Overall survival of TNBC patients was significantly shorter in the high-risk group than in the low-risk group for both the training and validation cohorts. Using the Kaplan-Meier curves and ROC curves, we demonstrated the accuracy of the prognostic model. Multivariate Cox regression analysis was used to verify risk score as independent predictor. Then a nomogram was proposed to predict 1-, 3-, and 5-year survival for TNBC patients. The calibration curves showed great accuracy of the model for survival prediction. Finally, we found that depletion of EIF4EBP1, one of ARGs in our model, significantly reduced cell proliferation and metastasis of TNBC cells. Conclusion: An autophagy-related prognosis model in TNBCs was constructed using ARGs signature containing CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74 and VAMP3. It could serve as an independent prognostic biomarker in TNBC.

scholarly journals Differential expression of NDC80, kinetochore complex component in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Complex Component ◽  
Ductal Cells

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding NDC80, kinetochore complex component, NDC80, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). NDC80 was also differentially expressed in bulk tumor in human breast cancer (3). NDC80 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of NDC80 in primary tumors of the breast was correlated with overall survival in patients with basal-like and luminal A subtype cancer, while within triple negative breast cancer, primary tumor expression of NDC80 was correlated with overall survival in patients with basal-like 1 subtype disease. NDC80 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

scholarly journals Comprehensive In Silico Analysis of a Novel Serum Exosome-Derived Competitive Endogenous RNA Network for Constructing a Prognostic Model for Glioblastoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zihao Wang ◽  
Xin Ji ◽  
Lu Gao ◽  
Xiaopeng Guo ◽  
Wei Lian ◽  
...  
Keyword(s):  
Prognostic Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Treatment Strategies ◽  
Differentially Expressed ◽  
Clinicopathological Parameters ◽  
Survival Prediction ◽  
Regression Analyses ◽  
Cerna Network ◽  
Competitive Endogenous Rna

PurposeGlioblastoma (GBM) is one of the most aggressive brain tumors with high mortality, and tumor-derived exosomes provide new insight into the mechanisms of GBM tumorigenesis, metastasis and therapeutic resistance. We aimed to establish an exosome-derived competitive endogenous RNA (ceRNA) network for constructing a prognostic model for GBM.MethodsWe obtained the expression profiles of long noncoding RNAs (lncRNAs), miRNAs, and mRNAs from the GEO and TCGA databases and identified differentially expressed RNAs in GBM to construct a ceRNA network. By performing lasso and multivariate Cox regression analyses, we identified optimal prognosis-related differentially expressed lncRNAs (DElncRNAs) and generated a risk score model termed the exosomal lncRNA (exo-lncRNA) signature. The exo-lncRNA signature was subsequently validated in the CGGA GBM cohort. Finally, a novel prognostic nomogram was constructed based on the exo-lncRNA signature and clinicopathological parameters and validated in the CGGA external cohort. Based on the ceRNA hypothesis, oncocers were identified based on highly positive correlations between lncRNAs and mRNAs mediated by the same miRNAs. Furthermore, regression analyses were performed to assess correlations between the expression abundances of lncRNAs in tumors and exosomes.ResultsA total of 45 DElncRNAs, six DEmiRNAs, and 38 DEmRNAs were identified, and an exosome-derived ceRNA network was built. Three optimal prognostic-related DElncRNAs, HOTAIR (HR=0.341, P<0.001), SOX21-AS1 (HR=0.30, P<0.001), and STEAP3-AS1 (HR=2.47, P<0.001), were included to construct the exo-lncRNA signature, which was further proven to be an independent prognostic factor. The novel prognostic nomogram was constructed based on the exo-lncRNA signature, patient age, pharmacotherapy, radiotherapy, IDH mutation status, and MGMT promoter status, with a concordance index of 0.878. ROC and calibration plots both suggested that the nomogram had beneficial discrimination and predictive abilities. A total of 11 pairs of prognostic oncocers were identified. Regression analysis suggested excellent consistency of the expression abundance of the three exosomal lncRNAs between exosomes and tumor tissues.ConclusionsExosomal lncRNAs may serve as promising prognostic predictors and therapeutic targets. The prognostic nomogram based on the exo-lncRNA signature might provide an intuitive method for individualized survival prediction and facilitate better treatment strategies.

scholarly journals Differential expression of cell division cycle associated 2 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cell Division ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cell division cycle associated 2, CDCA2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CDCA2 was also differentially expressed in bulk tumor in human breast cancer (3). CDCA2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CDCA2 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of CDCA2 was correlated with overall survival in patients with basal-like 1, mesenchymal stem-like, and luminal androgen receptor subtype disease. CDCA2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

scholarly journals Differential expression of structural maintenance of chromosomes 4 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells ◽  
Structural Maintenance Of Chromosomes

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding structural maintenance of chromosomes 4, SMC4, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). SMC4 was also differentially expressed in bulk tumor in human breast cancer (3). SMC4 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of SMC4 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of SMC4 was correlated with overall survival in patients with mesenchymal, mesenchymal stem-like, and luminal androgen receptor subtype disease. SMC4 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

Sign in / Sign up

Export Citation Format

Share Document