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.

Effect of TCHL-based therapy on immune cell content in on-treatment, neoadjuvant-treated HER2-positive breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 583-583
Author(s):  
Niamh M. Keegan ◽  
Sinead Toomey ◽  
Joanna Fay ◽  
Stephen F. Madden ◽  
Bruce Moran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Cell Populations ◽  
Breast Cancer Patients ◽  
Myeloid Dendritic Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
The Impact ◽  
Positive Breast Cancer

583 Background: In the TCHL trial (NCT01485926) 78 women with HER2-positive breast cancer (BC) underwent neo-adjuvant treatment with either TCH (Docetaxel, Carboplatin, Trastuzumab) or TCHL (TCH + Lapatinib) therapy. Of the 78 patients, 24 consented to an optional on-treatment biopsy 20 days after 1 cycle of therapy. We analysed the impact of tumour infiltrating lymphocytes (TILs) on pathological complete response (pCR) and also determined the impact of TCH/TCHL therapy on immune cell modulation after 20 days of treatment. Methods: We assessed TIL and stromal lymphocytes (SL) counts using immunohistochemical staining with Haemotoxalyin+Eosin, AE1/AE3 and CD45 in formalin fixed paraffin embedded (FFPE) baseline biopsy samples and in fresh frozen (FF) biopsies taken 20-days post cycle 1 (Day-20) of TCH/TCHL. RNA libraries were generated, using the Truseq mRNA library prep kit on the Neoprep platform and sequenced on the NextSeq 500. We measured the transcriptomic profile of 8 pre and on-treatment sample pairs and then used the Microenvironment Cell Populations (MCP)-counter method to measure the abundance of 10 immune cell populations (T cells, CD8 T cells, cytotoxic lymphocytes, NK cells, B lineage, myeloid dendritic cells, neutrophils, endothelial cells and fibroblasts). Results: We found that higher baseline levels of TILs (p = 0.045) but not SL were associated with an increased likelihood of a patient achieving a pCR to TCH/L based therapy. We found in day 20 on-treatment biopsies of women that subsequently went onto have a pCR that levels of SLs but not TILs were significantly higher (p = 0.049) than in those women who did not have a pCR. Finally we found significant increases in the level of monocytes (p = 0.05) and fibroblasts (p = 0.01), but not other immune cell populations, in the day 20 on-treatment biopsies in comparison with the mutated pre-treatment biopsies. Conclusions: In our study baseline TILs but not SLs have a predictive role in the likelihood of a patient achieving a pCR. We also found that TCHL based therapy significantly altered both monocytes and fibroblasts, indicating a possible role for these immune subtypes in response to TCHL therapy.

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 Explainable Artificial Intelligence Reveals Novel Insight into Tumor Microenvironment Conditions Linked with Better Prognosis in Patients with Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3450
Author(s):  
Debaditya Chakraborty ◽  
Cristina Ivan ◽  
Paola Amero ◽  
Maliha Khan ◽  
Cristian Rodriguez-Aguayo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Artificial Intelligence ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Immune Cell ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Inflection Points ◽  
Explainable Artificial Intelligence

We investigated the data-driven relationship between immune cell composition in the tumor microenvironment (TME) and the ≥5-year survival rates of breast cancer patients using explainable artificial intelligence (XAI) models. We acquired TCGA breast invasive carcinoma data from the cbioPortal and retrieved immune cell composition estimates from bulk RNA sequencing data from TIMER2.0 based on EPIC, CIBERSORT, TIMER, and xCell computational methods. Novel insights derived from our XAI model showed that B cells, CD8+ T cells, M0 macrophages, and NK T cells are the most critical TME features for enhanced prognosis of breast cancer patients. Our XAI model also revealed the inflection points of these critical TME features, above or below which ≥5-year survival rates improve. Subsequently, we ascertained the conditional probabilities of ≥5-year survival under specific conditions inferred from the inflection points. In particular, the XAI models revealed that the B cell fraction (relative to all cells in a sample) exceeding 0.025, M0 macrophage fraction (relative to the total immune cell content) below 0.05, and NK T cell and CD8+ T cell fractions (based on cancer type-specific arbitrary units) above 0.075 and 0.25, respectively, in the TME could enhance the ≥5-year survival in breast cancer patients. The findings could lead to accurate clinical predictions and enhanced immunotherapies, and to the design of innovative strategies to reprogram the breast TME.

Tim-3 identifies exhausted follicular helper T cells in breast cancer patients

Immunobiology ◽  
2016 ◽  
Vol 221 (9) ◽  
pp. 986-993 ◽  
Author(s):  
Shiguang Zhu ◽  
Jun Lin ◽  
Guangdong Qiao ◽  
Xingmiao Wang ◽  
Yanping Xu
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Helper T Cells ◽  
Breast Cancer Patients ◽  
Follicular Helper T Cells ◽  
Follicular Helper

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.

scholarly journals ceRNA network development and tumour-infiltrating immune cell analysis of metastatic breast cancer to bone

2020 ◽  
Vol 24 ◽  
pp. 100304
Author(s):  
Shuzhong Liu ◽  
An Song ◽  
Xi Zhou ◽  
Zhen Huo ◽  
Siyuan Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Cell Analysis ◽  
Network Development ◽  
Cerna Network

Role of CD8+ T-cell infiltration in breast tumors of Black women compared to White women.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13608-e13608
Author(s):  
Yara Abdou ◽  
Kristopher Attwood ◽  
Song Yao ◽  
Ting-Yuan David Cheng ◽  
Elisa Bandera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Black Women ◽  
T Cell ◽  
Cell Density ◽  
Immune Cell ◽  
Beta Blockers ◽  
Breast Cancer Patients ◽  
T Cell Infiltration ◽  
Black Patients

e13608 Background: Literature regarding racial differences in tumor immune responses in breast cancer remains sparse. To address this research gap, we assessed CD8+ T-cells in breast tumor samples from the Women’s Circle of Health Study (WCHS) population of predominantly Black breast cancer patients. We characterized and compared the density of CD8+ T cells, their prognostic value and their association with pharmacologic beta-blockers. Prior studies suggest that reducing adrenergic signaling through beta blockers can stimulate CD8+ T-cells. Methods: Tumor-infiltrating CD8+ T-cells were assessed by IHC staining of tissue microarray cores from 688 breast cancer patients, including 550 Blacks and 138 Whites. CD8+ T cells were scored with digital image analysis. Comparisons of demographic and clinical variables (including CD8+ T cell density) were made using the Mann-Whitney U or Kruskal-Wallis and Fisher’s exact tests. Associations with overall survival (OS) and disease-specific (DSS) survival were evaluated using the log-rank test of Cox regression. Analyses were performed in the overall sample and by disease sub-type. Results: Higher CD8+ T cell density was seen in Black women compared to White, with mean values of 756.2/mm2 and 292.4/mm2 respectively (p < 0.001). Within the overall population and in black women, CD8+ T cell density was significantly higher in younger patients, patients with high grade, and ER negative tumors. No significant associations were observed between CD8+ T cell density and OS or DSS. However, when stratified by subtype, Black patients with triple negative breast cancer and high CD8+ T cell density showed a trend towards improved OS in comparison to patients with low CD8+ T cell density (p = 0.065). 170 patients with information on beta blocker usage were analyzed. No significant associations were noted between CD8+ T cell density and beta blocker use. Conclusions: We observe a significantly higher CD8+ T cell density in Blacks compared to Whites, but this does not confer a survival advantage. Additionally, beta-blockers did not seem to enhance CD8+ T cell infiltration in tumors from Black patients. Our data raise the possibility that distinct mechanisms of immune cell action may occur in different racial groups. Future studies are needed to determine the functional properties of CD8+ T cells in Black women and to characterize additional immune cell subtypes that may also play a role.

Overexpressed FAM166B Predicts Favorable Prognosis and Associated With Metabolic Pathways and Tumor Immune Infiltrates in BRCA

2021 ◽  
Author(s):  
Yi Zhou ◽  
Huiqin Zhu ◽  
Gao He ◽  
Hongfei Zhang ◽  
Xuyu Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Immune Therapy ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Protein Coding ◽  
Kaplan Meier ◽  
Cox Analysis

Abstract Background: Breast cancer is one of the most common and lethal cancer worldwide. Though surgery, chemotherapy, endocrine therapy and immune therapy have boost patients' survival rate, to establish more molecular biomarkers that can detect the early metastasis and shed a light on breast cancer treatment still requires efforts. Based on previous studies, adipose tissue had a metabolic crosstalk in breast cancer. FAM166B is a protein-coding gene which was reported to be found in adipose tissues. Yet whether FAM166B has a role in breast cancer had not been determined.Methods: In this study, 1109 BRCA patients and 113 adjacent cancer samples and clinical characteristics data were downloaded from TCGA data portal, R software and Strawberry Perl were used for all pre-processing processes. Kaplan-Meier plotter, univariate and multivariate Cox analysis were used to investigate FAM166B potential in BRCA prognosis. GSEA was performed to investigate the biological function of FAM166B. Furthermore, TIMER was utilized to identify the association between FAM166B and tumor-infiltrating immune cells.Results: We found out increased FAM166B expression correlates with better prognosis in BRCA. By conducting Multivariate Cox analysis, we draw a conclusion that FAM166B could be an independent prognosis factor. Moreover, the GSEA revealed that FAM166B could possibly restrain the cell metabolism and glucose converting pathways. Also, a high expression of FAM166B was correlated with increased immune infiltration levels like CD4+ T cells and decreased macrophages, especially in luminal and basal breast cancers. Conclusion: Our study illustrated that FAM166B is an independent prognostic factor in BRCA. A high expression of FAM166B indicates a better prognosis of breast cancer patients and it may restrain the tumor cell metabolism and likely play a role in immune cell infiltration.

scholarly journals Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients

2011 ◽  
Vol 107 (5) ◽  
pp. 712-718 ◽  
Author(s):  
S. R. Zhuang ◽  
H. F. Chiu ◽  
S. L. Chen ◽  
J. H. Tsai ◽  
M. Y. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Placebo Group ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Immune Cell ◽  
Chinese Herbs ◽  
Controlled Study ◽  
Breast Cancer Patients ◽  
Chinese Medicinal Herb

Rose geranium (Pelargonium graveolens, Geraniaceae) has anti-cancer and anti-inflammatory properties, and promotes wound healing. Similarly,Ganoderma tsugae(Ganodermataceae),Codonopsis pilosula(Campanulaceae) andAngelica sinensis(Apiaceae) are traditional Chinese herbs associated with immunomodulatory functions. In the present study, a randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, RG-CMH, which represents a mixture of rose geranium and extracts ofG. tsugae, C. pilosula and A. sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy. A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group. RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. However, these differences between the two groups were not statistically significant. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.

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