scholarly journals Tumor Microenvironment Subtypes and Immune-Related Signatures for the Prognosis of Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yiqun Han ◽  
Jiayu Wang ◽  
Binghe Xu
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Tumor Microenvironment ◽  
Prognostic Model ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
The Cancer Genome Atlas ◽  
Molecular Heterogeneity ◽  
Consensus Clustering ◽  
Breast Cancer Patients

Objective. To better understand the immune-related heterogeneity of tumor microenvironment (TME) and establish a prognostic model for breast cancer in clinical practice. Methods. For the 2620 breast cancer cases obtained from The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium, the CIBERSORT algorithm was performed to identify the immunological pattern, which underwent consensus clustering to curate TME subtypes, and biological profiles were explored by enrichment analysis. Random forest analysis, least absolute shrinkage, and selection operator analysis, in addition to uni- and multivariate COX regression analyses, were successively employed to precisely select the significant genes with prediction values for the introduction of the prognostic model. Results. Three TME subtypes with distinct molecular and clinical features were identified by an unsupervised clustering approach, of which the molecular heterogeneity could be the result of cell cycle dysfunction and the variation of cytotoxic T lymphocyte activity. A total of 15 significant genes were proposed to construct the prognostic immune-related score system, and a predictive model was established in combination with clinicopathological characteristics for the survival of breast cancer patients. For immunological signatures, proactivity of CD8 T lymphocytes and hyperangiogenesis could be attributed to heterogeneous survival profiles. Conclusions. We developed and validated a prognostic model based on immune-related signatures for breast cancer. This promising model is justified for validation and optimized in future clinical practice.

scholarly journals Tumor microenvironment subtypes and immune-related signatures for the prognosis of breast cancer

2020 ◽  
Author(s):  
Yiqun Han ◽  
Jiayu Wang ◽  
Binghe Xu
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Cancer Patients ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cell Types ◽  
Well Performance ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis

Abstract To better understand the heterogeneity of tumor microenvironment (TME) and establish a prognostic model for breast cancer in clinical practice, the leukocyte infiltrations of 22 cell types of interest from 2620 breast cancer patients were quantitatively estimated using deconvolution algorithms, and three TME subtypes with distinct molecular and clinical features were identified by unsupervised clustering approach. Then, we carried out systematic analyses to illustrate the contributing mechanisms for differential phenotypes, which suggested that the divergences were distinguished by cell cycle dysfunction, variation of cytotoxic T lymphocytes activity. Next, through dimensionally reduction and selection based on random-forest analysis, least absolute shrinkage and selection operator (LASSO) analysis, and uni- and multivariate COX regression analysis, a total of 15 significant genes were proposed to construct the prognostic immune-related score (pIRS) system and, in combinations with clinicopathological characteristics, a predictive model was ultimately built with well performance for survival of breast cancer patients. Comparative analyses demonstrated that proactivity of CD8 T lymphocytes and hyper-angiogenesis could be attributed to distinct prognostic outcomes. In conclusion, we retrieved three TME phenotypes and the curated prognostic model based on pIRS system for breast cancer. This model is justified for validation and optimized in the coming future.

scholarly journals Comprehensive Analysis of the Immune and Prognostic Implication of TRIM8 in Breast Cancer

2021 ◽  
Author(s):  
Cheng Yan ◽  
Qingling Liu ◽  
Mingkun Nie ◽  
Wei Hu ◽  
Ruoling Jia
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Mrna Levels ◽  
Breast Cancer Patients ◽  
Prognostic Signature ◽  
Normal Tissues

Abstract Background: Breast cancer remains one of most lethal illnesses for female and the most common malignancies among women, making it important to discover novel biomarkers and therapeutic targets for breast cancer. Immunotherapy has become a promising therapeutic tool for breast cancer. The role of TRIM8 in breast cancer has rarely been reported. Method: Here we identified TRIM8 expression and its potential functions on survival in patients with breast cancer using TCGA (The cancer genome atlas), GEO (Gene expression omnibus) database and METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Then, TIMER and TISIDB databases were used to investigate the correlations between TRIM8 mRNA levels and immune characteristics. Using stepwise cox regression, we established an immune prognostic signature based on five differentially expression immune-related genes (DE-IRGs). Finally, a nomogram, accompanied by a calibration curve was proposed to predict 1-, 3-, and 5-year survival for breast cancer patients. Results: We found that TRIM8 expression was dramatically lower in breast cancer tissues in comparison with normal tissues. Lower TRIM8 expression was related with worse prognosis in breast cancer. TIMER and TISIDB analysis showed that there were strong correlations between TRIM8 expression and immune characteristics. The receiver operating characteristic (ROC) curve confirmed the good performance in survival prediction, showing good accuracy of the immune prognostic signature. We demonstrated the model usefulness of predictions by nomogram and calibration curves. Our findings indicated that TRIM8 might be a potential link between progression and prognosis survival of breast cancer.Conclusion: This is a comprehensive study to reveal that TRIM8 may serve as a potential prognostic biomarker associating with immune characteristics and provide a novel therapeutic target for the treatment of breast cancer.

scholarly journals Identified metabolic related genes to construct a prognostic model of Breast cancer patients

2020 ◽  
Author(s):  
Yu-Yuan Ma ◽  
Han Wang ◽  
Jie Qi ◽  
Jie Zhu ◽  
Yue-Qing Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Model ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Earth Observations ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Geo Database

Abstract Background: More and more evidence confirms that there are many metabolic disorders in the tumor. The occurrence and development of breast cancer (BC) is closely related to metabolism. Methods: A metabolic related genes table was obtained by the Kyoto Encyclopedia of Genes and Genomes (KEGG) related metabolic pathway. The edgeR package was used to identify differentially expressed genes (DEGs) of The Cancer Genome Atlas (TCGA) breast cancer. We established a prognostic model by univariate Cox regression analysis and lasso-penalized Cox regression. The validation prognostic model was built through the Group on Earth Observations (GEO) database. Use the nomogram and Receiver Operating Characteristic (ROC) curve to verify the accuracy of models. Result: We identified 178 DEGs and 14 prognostic-related genes to construct a prognostic model. In the TCGA prognostic model and the GEO validation prognostic model, patients were divided into high riskscore group and low riskscore group, the high riskscore group had worse prognosis.Conclusion: We constructed a prognostic model of metabolic related genes and verified the feasibility and accuracy of the model. It is hoped that the model can provide a basis and biomarker for breast cancer related metabolic therapy and prognosis.

scholarly journals Developing ZNF Gene Signatures Predicting Radiosensitivity of Patients with Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Derui Yan ◽  
Mingjing Shen ◽  
Zixuan Du ◽  
Jianping Cao ◽  
Ye Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
The Relationship

Adjuvant radiotherapy is one of the main treatment methods for breast cancer, but its clinical benefit depends largely on the characteristics of the patient. This study aimed to explore the relationship between the expression of zinc finger (ZNF) gene family proteins and the radiosensitivity of breast cancer patients. Clinical and gene expression data on a total of 976 breast cancer samples were obtained from The Cancer Genome Atlas (TCGA) database. ZNF gene expression was dichotomized into groups with a higher or lower level than the median level of expression. Univariate and multivariate Cox regression analyses were used to evaluate the relationship between ZNF gene expression levels and radiosensitivity. The Molecular Taxonomy Data of the International Federation of Breast Cancer (METABRIC) database was used for validation. The results revealed that 4 ZNF genes were possible radiosensitivity markers. High expression of ZNF644 and low expression levels of the other 3 genes (ZNF341, ZNF541, and ZNF653) were related to the radiosensitivity of breast cancer. Hierarchical cluster, Cox, and CoxBoost analysis based on these 4 ZNF genes indicated that patients with a favorable 4-gene signature had better overall survival on radiotherapy. Thus, this 4-gene signature may have value for selecting those patients most likely to benefit from radiotherapy. ZNF gene clusters could act as radiosensitivity signatures for breast cancer patients and may be involved in determining the radiosensitivity of cancer.

scholarly journals DNA Methylation Based Molecular Subtypes Predict Prognosis in Breast Cancer Patients

2021 ◽  
Vol 28 ◽  
pp. 107327482098851
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Yan Zhou
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Molecular Subtypes ◽  
Methylation Status ◽  
The Cancer Genome Atlas ◽  
Training Dataset ◽  
Consensus Clustering ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Novel Biomarkers

Background: Epigenetic changes are tightly linked to tumorigenesis development and malignant transformation’ However, DNA methylation occurs earlier and is constant during tumorigenesis. It plays an important role in controlling gene expression in cancer cells. Methods: In this study, we determining the prognostic value of molecular subtypes based on DNA methylation status in breast cancer samples obtained from The Cancer Genome Atlas database (TCGA). Results: Seven clusters and 204 corresponding promoter genes were identified based on consensus clustering using 166 CpG sites that significantly influenced survival outcomes. The overall survival (OS) analysis showed a significant prognostic difference among the 7 groups (p<0.05). Finally, a prognostic model was used to estimate the results of patients on the testing set based on the classification findings of a training dataset DNA methylation subgroups. Conclusions: The model was found to be important in the identification of novel biomarkers and could be of help to patients with different breast cancer subtypes when predicting prognosis, clinical diagnosis and management.

scholarly journals Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9621
Author(s):  
Shanliang Zhong ◽  
Huanwen Chen ◽  
Sujin Yang ◽  
Jifeng Feng ◽  
Siying Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Risk Group ◽  
Breast Cancer Survival ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Breast Cancer Patients ◽  
Prognostic Signature

We aimed to identify prognostic signature based on autophagy-related genes (ARGs) for breast cancer patients. The datasets of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to construct multiple-ARG risk signature. In total, 32 ARGs were identified as differentially expressed between tumors and adjacent normal tissues based on TCGA. Six ARGs (IFNG, TP63, PPP1R15A, PTK6, EIF4EBP1 and NKX2-3) with non-zero coefficient were selected from the 32 ARGs using LASSO regression. The 6-ARG signature divided patients into high-and low-risk group. Survival analysis indicated that low-risk group had longer survival time than high-risk group. We further validated the 6-ARG signature using dataset from GEO and found similar results. We analyzed the associations between ARGs and breast cancer survival in TCGA and nine GEO datasets, and obtained 170 ARGs with significant associations. EIF4EBP1, FOS and FAS were the top three ARGs with highest numbers of significant associations. EIF4EBP1 may be a key ARG which had a higher expression level in patients with more malignant molecular subtypes and higher grade breast cancer. In conclusion, our 6-ARG signature was of significance in predicting of overall survival of patients with breast cancer. EIF4EBP1 may be a key ARG associated with breast cancer survival.

scholarly journals Five Crucial Prognostic-Related Autophagy Genes Stratified Female Breast Cancer Patients Aged 40-60 Years

2020 ◽  
Author(s):  
Xiaolong Li ◽  
Hengchao Zhang ◽  
Jingjing Liu ◽  
Ping Li ◽  
Yi Sun
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Prognostic Model ◽  
Cox Regression ◽  
Survival Curve ◽  
Predictive Ability ◽  
Clinicopathological Parameters ◽  
Risk Level ◽  
Lasso Regression ◽  
Breast Cancer Patients

Abstract Background : Autophagy is closely related to the progression of breast cancer. The aim at this study is to establish a prognostic-related model comprised of hub autophagy-genes (AGs ) to assess patient prognosis. Simultaneously, the model can guide clinicians to make up individualized strategies and stratify patients aged 40-60 years based on risk level. Methods : The hub AGs were identified with univariate COX regression and LASSO regression. The functions and alterations of these selected AGs were analyzed as well. Moreover, the multivariate COX regression and correlation analysis between hub AGs and clinicopathological parameters were done. Results : Totally, 33 prognostic-related AGs were obtained from the univariate COX regression (P<0.05 ) . SERPINA1 , HSPA8 , HSPB8 , MAP1LC3A , and DIRAS3 were identified to constitute the prognostic model by the LASSO regression . The survival curve of patients in high-risk and in low-risk group was statistically significant (P<0.05 ) . The 3-year and 5-year ROC displayed that their AUC value reached 0.762 and 0.825 , respectively . Stage and risk score were independent risk factors relevant about prognosis . RB1CC1 , RPS6KB1 , and BIRC6 were identified as the most predominant mutant genes . It was found that AGs were mainly involved in regulating the endopeptidases synthesis and played important roles in ErbB signal pathway . SERPIN1 , risk score were closely related to stage (P<0.05 ) ; HSPA8, risk score were closely related to T stag (P<0.05 ) ; HSPB8 was closely related to N stag (P<0.05 ). Conclusions : Our prognostic model had relatively robust predictive ability on prognosis for patients aged 40-60 years. If stage was added into 3 the prognostic model, the predictive ability would be more powerful.

Identification and Validation of a Novel 16-Gene Prognostic Signature for Patients with Breast Cancer

2021 ◽  
Author(s):  
Zhenhua Zhong ◽  
Wenqiang Jiang ◽  
Jing Zhang ◽  
Zhanwen Li ◽  
Fengfeng Fan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
Rna Degradation ◽  
The Cancer Genome Atlas ◽  
Gene Score ◽  
Disease Heterogeneity ◽  
Cox Regression Analysis ◽  
Risk Of Death

Abstract Background: Despite increased early diagnosis and improved treatment in breast cancer (BRCA) patients, prognosis prediction is still a challenging task due to the disease heterogeneity. This study was to identify a novel gene signature that can accurately evaluate BRCA patient survival. Methods: The gene expression and clinical data of BRCA patients were collected from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of BRCA International Consortium (METABRIC) databases. Genes associated with prognosis were determined by Kaplan–Meier survival analysis and multivariate Cox regression analysis. A prognostic 16-gene score was established with linear combination of 16 genes. The prognostic value of the signature was validated in the METABRIC dataset. Gene expression analysis was performed to investigate the diagnostic values of 16 genes. Results: The 16-gene score was associated with shortened overall survival in BRCA patients independently of clinicopathological characteristics. The signalling pathways of cell cycle, oocyte meiosis, RNA degradation, progesterone mediated oocyte maturation and DNA replication were the top five most enriched pathways in the high 16-gene score group. The 16-gene nomogram incorporating the survival‐related clinical factors showed improved prediction accuracies for 1-year, 3-year and 5‐year survival (area under curve [AUC] = 0.91, 0.79 and 0.77 respectively). MORN3, IGJ, DERL1 exhibited high accuracy in differentiating BRCA tissues from normal breast tissues (AUC > 0.80 for all cases). Conclusions: The 16-gene profile provides novel insights into the identification of BRCA with a high risk of death, which eventually guides treatment decision making.

Expression patterns and a prognostic model of m6A-associated regulators in prostate adenocarcinoma

2020 ◽  
Vol 14 (18) ◽  
pp. 1717-1731
Author(s):  
Song Ou-Yang ◽  
Ji-Hong Liu ◽  
Qin-Zhang Wang
Keyword(s):  
Prognostic Model ◽  
Cox Regression ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Prostate Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Cox Regression Analysis ◽  
Clinical Biomarkers

Aim: To study the expression patterns and prognostic value of the m6A-associated regulators in prostate adenocarcinoma (PRAD). Materials & methods: The mRNA expression and clinical data were downloaded from ‘The Cancer Genome Atlas database’. The m6A-associated variants were downloaded from m6AVar database, and combined with 14 common m6A regulators for subsequent analysis. One-way analysis of variance, univariate Cox regression analysis and least absolute shrinkage and selection operator algorithm were successively applied to obtain the ultimate regulators and prognostic model. Finally, consensus clustering, protein–protein interaction (PPI) and enrichment analysis were performed. Result: Nine regulators were obtained. PRAD patients could be classified into two risk groups and subclasses with significant survival differences by the prognostic model and consensus clustering, respectively. Conclusion: All these nine regulators were related to prognosis in PRAD, and could be used as clinical biomarkers.

scholarly journals A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0249174
Author(s):  
Lili Zhu ◽  
Kang Cui ◽  
Lanling Weng ◽  
Pu Yu ◽  
Yabing Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Cox Regression ◽  
Early Stage ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Breast Cancer Patients

Background Breast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients. Methods Systematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores. Results Our study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model. Conclusion Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.

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