scholarly journals Risk Signature of Cancer-Associated Fibroblast–Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunxiao Sun ◽  
Siwei Wang ◽  
Yuchen Zhang ◽  
Fan Yang ◽  
Tianyu Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Genome Duplication ◽  
Driver Mutations ◽  
Intratumor Heterogeneity ◽  
Clinical Prognosis ◽  
Cancer Associated Fibroblast ◽  
The Status ◽  
Prognostic Prediction ◽  
The Relationship

Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.

scholarly journals A Novel Platelet-Related Gene Signature for Predicting the Prognosis of Triple-Negative Breast Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Jindong Xie ◽  
Yutian Zou ◽  
Feng Ye ◽  
Wanzhen Zhao ◽  
Xinhua Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Clinical Prognosis

Regarded as the most invasive subtype, triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) proteins. Platelets have recently been shown to be associated with metastasis of malignant tumors. Nevertheless, the status of platelet-related genes in TNBC and their correlation with patient prognosis remain unknown. In this study, the expression and variation levels of platelet-related genes were identified and patients with TNBC were divided into three subtypes. We collected cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, we constructed a seven-gene signature which classified the two cohorts of patients with TNBC into low- or high-risk groups. Patients in the high-risk group were more likely to have lower survival rates than those in the low-risk group. The risk score, incorporated with the clinical features, was confirmed as an independent factor for predicting the overall survival (OS) time. Functional enrichment analyses revealed the involvement of a variety of vital biological processes and classical cancer-related pathways that could be important to the ultimate prognosis of TNBC. We then built a nomogram that performed well. Moreover, we tested the model in other cohorts and obtained positive outcomes. In conclusion, platelet-related genes were closely related to TNBC, and this novel signature could serve as a tool for the assessment of clinical prognosis.

scholarly journals CD52 is a prognostic biomarker and correlated with immune features in breast cancer

2020 ◽  
Author(s):  
Jianxin Wang ◽  
Yang Liu ◽  
Zhuowen Yang ◽  
Yang Sui ◽  
Jie Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Clinical Data ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Aggressive Cancer ◽  
Immunotherapy Target ◽  
Tcga Dataset ◽  
Prognostic Prediction ◽  
The Relationship

Abstract Background: Breast cancer (BRCA) is the most commonly diagnosed cancer of women, which is aggressive cancer and has a mortality rate. CD52 and its monoclonal antibody (Alemtuzumab) play a critical role in inflammatory diseases, but the relationship between CD52 and BRCA is not clear.Methods: We first used the random forest algorithm to find the most critical genes related to the prognosis of BRCA patients. Then, according to the analysis of RNA sequence and clinical data of the TCGA dataset, we explored the relationship between CD52 with immune response-related pathways and immune metagenes. The pan-cancer analysis shows the importance of CD52 in a variety of tumorsResults:CD52 was related to the prognosis of BRCA patients (p < 0.001). Subsequent analysis based on RNA-seq and clinical data from the TCGA dataset revealed that CD52 is positively correlated with immune response-related pathways and immune metagenes. TIMER analysis showed that CD52 expression was positively correlated with immune infiltrating levels of B, CD4+ T, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in BRCA (r = 0.466, r = 0.645, r = 0.483, r = 0.149, r= 0.542,r = 0.665, respectively; p < 0.001). CpG sites (cg16068833, cg19743891, cg19743891, cg16664472, cg19677267, cg22517705, and cg27430637) were negatively correlated with CD52 expression (r = -0.662, r = -0.629, r =- 0.598, r = -0.519, r= -0.492, r = -0.445, respectively; p < 0.001). Furthermore, the expression of CD52 was significantly correlated with the following pathological stages (T stage, N stage, and survival state; p=0.024, p=0.047, and p=0.007, respectively). The results of the pan-cancers study suggest that CD52 may play an important role in the occurrence, development, and prognosis of multiple tumors.Conclusions: These findings suggested that CD52 is a promising immunotherapy target and prognostic prediction value for BRCA.

scholarly journals Phytoestrogens and Breast Diseases: A Matter of Concern for the Gynecologist

2020 ◽  
pp. 4-9
Author(s):  
Sadaf Alipour ◽  
Amirhossein Eskandari
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
General Population ◽  
Breast Cancer Survivors ◽  
Estrogenic Activity ◽  
Structural Similarity ◽  
Breast Diseases ◽  
High Risk Women ◽  
High Doses ◽  
The Relationship

Background: This study is the last part of a quadruple series investigating the relationship between breast disorders and the consumption of exogenous sex hormones. Due to the structural similarity of phytoestrogens to estrogen and the confusion associated with their possible estrogenic activity in the breast, this part aims at reviewing of the literature on the relationship between phytoestrogens and breast disorders. Methods: We carried out a thorough search of the existing literature using appropriate keywords with the aim of finding systematic reviews, reviews, cohort studies and clinical trials regarding the effects of phytoestrogens on the breast in the general population, breast cancer survivors, women at high risk of breast cancer and those with benign breast diseases. Results: Many studies have approached the relationship between phytoestrogens and the risk of breast cancer or recurrence of the disease. Also, a few studies have considered the effects of phytoestrogens on benign breast disorders, BRCA genes, and the risk of breast cancer in high risk women. However, the variety of studies and the retrospective nature of many of them make it impossible to draw definite conclusions. Conclusion: Existing data generally supports the safety of phytoestrogen consumption regarding the risk of breast cancer in the general population, in women with benign breast disorders, in those at risk of breast cancer, and even in survivors of the cancer. However, due to insufficient evidence, prescription of high doses of phytoestrogens is still not recommended.

scholarly journals The relationship of breast density in mammography and magnetic resonance imaging in high-risk women and women with breast cancer

2015 ◽  
Vol 39 (6) ◽  
pp. 987-992 ◽  
Author(s):  
Marissa Albert ◽  
Freya Schnabel ◽  
Jennifer Chun ◽  
Shira Schwartz ◽  
Jiyon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Resonance Imaging ◽  
High Risk ◽  
Magnetic Resonance ◽  
Breast Density ◽  
Resonance Imaging ◽  
High Risk Women ◽  
Relationship Of ◽  
The Relationship

The relationship between tumor markers and histopathologic and demographic features of patients with breast cancer and their distinctive role in metastatic process.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11540-e11540
Author(s):  
Kubra Aydin ◽  
Meliha Melin Uygur ◽  
Hatice Odabas ◽  
Taner Korkmaz ◽  
Nurgul Yasar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Markers ◽  
Roc Analysis ◽  
Hormone Receptors ◽  
Breast Cancer Diagnosis ◽  
The Status ◽  
Metastatic Process ◽  
Randomised Controlled ◽  
The Relationship

e11540 Background: Tumor marker monitoring is generally performed by the physicians, although in many guidelines, it has not been recommended for breast cancer. In this study, we aimed to research the role of CEA and CA15.3 levels in metastatic process. Methods: In between years 2000 January and 2011 August, the documents of 482 female patients followed by breast cancer diagnosis in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital, were evaluated retrospectively. Results: To determine the role of CEA and CA15.3 levels in evaluation of metastatic process, ROC analysis was performed and its cut-off values were 1.3 ng/ml and 14 U/ml, respectively. Sensitivities of CA15.3 and CEA levels were detected as 83.33% and 87.50%; specificities were 40.80% and 41.14%, respectively. Evaluation of the relationship between CEA and CA15.3 levels and the status of hormone receptors by ROC analysis showed the cut-off values as 26 U/ml and 1,6 ng/ml, respectively. In determination of endocrine sensitivity, the sensitivities of tumor markers elevation were 88.17% and 54.12%, respectively. Their specificities were 26.92% and 73.08%. CEA level elevation in hormone sensitive patients was statistically significant (p: 0.007). When sensitivity and specificity of CA15.3 and CEA levels on detection of c-erbB2 positivity were evaluated by ROC analysis, cut-off values were determined as 17 U/ml and 1,7 ng/ml. Sensitivities of these distinctive cut-off values were found as 58.8% and 71.15% and specificities were 60% and 51.67% (p: 0.017). When the relation between CA15.3 and CEA levels and node involvement was evaluated by ROC analysis, cut-off values were respectively 16 U/ml and 0.9 ng/ml. Their sensitivities were 53.45% and 87.93% and specificities were 55.56% and 51.67%, respectively. Conclusions: The levels of tumor markers have been suggested to have a significant role in prognosis of the disease with respecttothe correlation between different histopathological and clinical features and tumor markers. Randomised controlled prospective studies planned and performed in this issue may clarify this uncertainity.

scholarly journals Connecting the Dots: Pre-existing Patterns of Gender Inequality and the Likelihood of Widespread and Systematic Sexual Violence

2017 ◽  
Vol 9 (1) ◽  
pp. 65-85 ◽  
Author(s):  
Sara E. Davies ◽  
Jacqui True
Keyword(s):  
High Risk ◽  
Sexual Violence ◽  
Gender Inequality ◽  
Gender Based Violence ◽  
The Status ◽  
Gender Based ◽  
And Gender ◽  
Connecting The Dots ◽  
The Relationship

In this article we explore the relationship between pre-existing patterns of gender inequality and the occurrence of widespread and systematic sexual and gender based violence (sgbv). We ask three questions: What do we know about the status of gender inequality in high-risk situations prior to the outbreak of atrocities (which include sgbv)? What can be done to understand the relationship between systemic gender inequality and the use of sexual violence in the particular high-risk situations? And what long-term approaches are necessary to prevent sgbv?

Expression of PD-L1 in Relation to Intrinsic Molecular Subtypes of Breast Cancer in Hainan Free Trade Port, China

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Feng CD ◽  
◽  
Zhang Y ◽  
Xu ZP ◽  
Gao BY ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Histological Grade ◽  
Expression Level ◽  
Luminal A ◽  
Her2 Positive ◽  
Clinical Prognosis ◽  
Female Patients ◽  
Significant Difference ◽  
The Relationship

Background: Intrinsic molecular subtype and histological grade are closely related to clinical prognosis in breast cancer. However, their relationship with Programmed Cell Death-Ligand 1 (PD-L1) expression is not very clear, particularly for Hainan Aboriginal patients. Herein, this research aims to reveal the relationship between PD-L1 expression and intrinsic molecular subtypes of breast cancer. Methods: 225 breast tumor samples from female patients were analyzed for PD-L1 expression using the Immunohistochemistry (IHC) method. The PDL1 expression level was detected by IHC and the relationship between the expression and clinical parameters was analyzed statistically. Results: Positive staining of PD-L1 was mainly found in the plasma membrane. In all cases, the positive rate was 12.0% (27/225). The PD-L1 expression level was significantly reduced in Luminal A subtype (the corrected ratio OR=0.15, p=0.04) whereas increased in HER2-positive subtype (OR=4.2, p=0.01). PD-L1 was significantly related to HER2-positive subtype (p<0.05) and histological grade 3 (p<0.05). There was statistically significant association between PD-L1 expression and metastasis (p=0.046), but not with the patient’s age, the tumor stage and menstruation (p>0.05). Moreover, there was a significant difference in the frequency of intrinsic subtypes between patients with positive and negative PD-L1 expression (p<0.001) among patients with metastasis. Conclusions: PD-L1 expression in breast cancer was positively correlated with HER2-positive subtype, higher pathological grade and metastasis of breast cancer, while negatively correlated with Luminal A in female patients in Hainan, China. PD-L1 may be a new independent marker to predict the prognostic factor in HER2-positive subtype breast cancer.

scholarly journals Immune Microenvironment-Related Genes Contribute to Clinical Prognosis in Patients with Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Dandan Feng ◽  
Jie Gao ◽  
Tianshu Yang ◽  
Yanli Ren ◽  
Wei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
High Risk ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Functional Enrichment ◽  
Clinical Prognosis ◽  
Network Analyses ◽  
Post Surgery

Abstract Background:Triple-negative breast cancer (TNBC) is a high-risk breast cancer subtype, which accounts for 15% to 20% of all breast cancers and generally has a poor prognosis. TNBC patients have high recurrence post-surgery and high risk of metastasis to other organs. The tumor microenvironment (TME) plays important roles in the carcinogenesis, development, and metastasis of tumors. Methods: This study aimed to investigate the effects of immune and stromal cell-related genes on TNBC prognosis. The ESTIMATE algorithm was used to calculate the immune/stromal scores of TNBC samples from the GEO database. The samples were divided into high- and low- score groups and the differential expression genes were identified using the limma package within R. Functional enrichment and protein-protein interaction (PPI) network analyses revealed that these genes are primarily involved in immune responses. Results:Survival analysis in both GSE21653 and KM-plotter website showed that 36 genes were significantly related to disease-free survival (DFS) of TNBC. Another survival analysis by R package survival in GSE58812 indicated that 14 genes of 36 were greatly interrelated to DFS of TNBC. Moreover, the expression levels of some of these genes were verified through immunohistochemical staining and RT-qPCR. Finally, four genes importantly associated with TNBC prognosis were identified with Cox-LASSO analysis. Time-dependent receiver-operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.95 for one-year survival rate, indicating the four genes performed very well for prognosis prediction. Conclusions:In conclusion, we identified four genes, including BIRC3, CD8A, GNLY and TRIM22, that are possibly associated with the TME and are potential prognostic and therapeutic markers of TNBC.

scholarly journals Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
JianBin Wu ◽  
Yuanyuan Zhu ◽  
MingMin Luo ◽  
Lei Li
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
The Relationship ◽  
Single Tumor

BackgroundImmunotherapy has emerged as a significant strategy to treat numerous tumors. The positive response to immunotherapy depends on the dynamic interaction between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Pyroptosis, inflammation-induced cell death, is intricately associated with several tumors. However, the relationship between pyroptosis and clinical prognosis, immune cell infiltration, and immunotherapy effect is unclear in breast cancer (BRCA).MethodsWe comprehensively evaluated 33 pyroptosis-related genes and systematically assessed the relationship between pyroptosis and tumor progression, prognosis, and immune cell infiltration. The PyroptosisScore was used to quantify the pyroptosis pattern of a single tumor patient. We then assessed their values for predicting prognoses and therapeutic responses in BRCA.ResultsThree different modes of PyroptosisClusters were determined. The characteristics of TME cell infiltration in these three PyroptosisClusters were highly consistent with three immunophenotypes of tumors, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Comprehensive bioinformatics analysis revealed that patients with a low PyroptosisScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, and were more sensitive to immunotherapy than those with a high PyroptosisScore.ConclusionsOur findings revealed the crucial role of pyroptosis in maintaining the diversity and complexity of TME. Pyroptosis is closely related to tumor progression, tumor prognosis, and immunotherapy response. Evaluating the PyroptosisScore of a single tumor can assist in understanding the characteristics of TME infiltration and lead to the development of more effective immunotherapy strategies.

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