scholarly journals Prognostic Value of MUC1 and its Correlation with Tumor-Infiltrating Immune Cells in Breast Cancer

2021 ◽  
Author(s):  
Xiaomin Xi ◽  
Yilin You ◽  
Weidong Huang ◽  
jicheng zhan
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
Muc1 Expression ◽  
Breast Cancer Patients ◽  
Gene Markers ◽  
Clinical Prognosis ◽  
Luminal B ◽  
Immune Infiltration

Abstract Background: MUC1 is a transmembrane glycoprotein, aberrantly glycosylated and overexpressed in a variety of epithelial cancers, and plays a crucial role in cancer progression, especially in breast cancer. It is also an essential regulator for immune functionality, but the mechanisms whereby it effects immune infiltration in breast cancer remain uncertain. Methods: In this research, MUC1 expression was analyzed by the Oncomine and TIMER database. The association between MUC1 and prognosis was evaluated by Kaplan-Meier plotter database. The correlations of MUC1 with immune infiltration and immunological markers were assessed by TIMER database. Results: We found that MUC1 expression was significantly correlated with outcomes in multiple cancers, with the effect being particularly pronounced in breast cancer. Pathologically, elevated MUC1 expression was related with worse prognosis depending on intrinsic subtypes, ER status, patient stage, lymph node and TP53 mutation status in breast cancer. Specifically, low level of MUC1 seemed to be more favorable to luminal B patients with systemic treatment. MUC1 expression had significant negative correlations with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, monocytes and dendritic cells (DCs) in breast cancer. Besides, MUC1 displayed strong regulations on macrophage polarization and diverse immunological gene markers. The patients with lower MUC1 and deeper immune infiltration predicted better prognosis. Conclusions: MUC1 is significantly associated with clinical prognosis and potentially plays an essential role in modulating cytotoxic T lymphocytes (CTLs), tumor associated macrophages (TAMs), natural killer cells (NK cells) and DCs in breast tumors. Collectively, MUC1 could be served as a valuable biomarker of predicting prognosis and immune infiltration for breast cancer patients.

scholarly journals Construction and Validation of an Immune Infiltration-Related Gene Signature for the Prediction of Prognosis and Therapeutic Response in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Peng ◽  
Haochen Yu ◽  
Yudi Jin ◽  
Fanli Qu ◽  
Haoyu Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Cancer Progression ◽  
Gene Signature ◽  
Significant Heterogeneity ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Immune Infiltration ◽  
Patient Prognosis ◽  
Prediction Of Prognosis

Breast cancer patients show significant heterogeneity in overall survival. Current assessment models are insufficient to accurately predict patient prognosis, and models for predicting treatment response are lacking. We evaluated the relationship between various immune cells and breast cancer and confirmed the association between immune infiltration and breast cancer progression. Different bioinformatics and statistical approaches were combined to construct a robust immune infiltration-related gene signature for predicting patient prognosis and responses to immunotherapy and chemotherapy. Our research found that a higher immune infiltration-related risk score (IRS) indicates that the patient has a worse prognosis and is not very sensitive to immunotherapy. In addition, a new nomogram was constructed based on the gene signature and clinicopathological features to improve the risk stratification and quantify the risk assessment of individual patients. Our study might contribute to the optimization of the risk stratification for survival and the personalized management of breast cancer.

scholarly journals Tissue-resident FOLR2+ macrophages associate with tumor-infiltrating CD8+ T cells and with increased survival of breast cancer patients

2021 ◽  
Author(s):  
Rodrigo Nalio Ramos ◽  
Yoann Missolo-Koussou ◽  
Yohan Gerber-Ferder ◽  
Christian Bromley ◽  
Mattia Bugatti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Macrophage Infiltration ◽  
Therapeutic Interventions ◽  
Breast Cancer Patients ◽  
Tumor Associated Macrophages ◽  
Tumor Associated Macrophage ◽  
Macrophage Subsets

SUMMARYMacrophage infiltration is a hallmark of solid cancers and overall macrophage infiltration is correlated with lower patient survival and resistance to therapy. However, tumor-associated macrophages are phenotypically and functionally heterogeneous. Specific tumor-associated macrophage subsets might be endowed with antagonistic role on cancer progression and on the development of anti-tumor immunity. For instance, monocyte-derived TREM2+ tumor-associated macrophages have pro-tumorigenic and immunosuppressive functions. Here, we identify a discrete population of FOLR2+ tumor-associated macrophages positively correlating with patient survival in breast cancer. FOLR2+ macrophages are evolutionarily conserved across species and populate human and murine healthy mammary gland. Moreover, FOLR2+ macrophages co-localize with lymphoid aggregates containing CD8+ T cells in breast cancer and across ten other types of cancers. This study highlights antagonistic roles for tumor-associated macrophage subsets and paves the way for subset-specific therapeutic interventions in macrophages-based cancer therapies.

scholarly journals CXCL2 as a Prognostic Marker in Breast Cancer is Associated with Immune Infiltration and Regulated by miR-215

2020 ◽  
Author(s):  
Jia-Xiang An ◽  
Ying-Ying Chen ◽  
Zhao-Sheng Ma ◽  
Wen-Jie Yu ◽  
Jin-Xi Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Time ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
The Impact ◽  
Kaplan Meier Plotter ◽  
Low Expression

Abstract Background: CXCL2 is a part of chemokine superfamily, which encodes secretory proteins involved in immune regulation and inflammation. The correlation between CXCL2 and prognosis of different cancers, tumor infiltrating lymphocytes are not clear. Methods: We analyzed the expression of CXCL2 and its effect on clinical prognosis through Oncomine database, Tumor Immune Estimation Resource (TIMER) website, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). TIMER and GEPIA were used to analyze the correlation between CXCL2 and the gene marker of immune infiltration. StarBase was used to predict the miRNA that may regulate CXCL2. The relationship between miR-532-5p and CXCL2 was detected by qRT-PCR. Kaplan-Meier plotter was used to evaluate the impact of miR-532-5p on clinical prognosis. Results: PrognoScan, Kaplan-Meier plotter and GEPIA database analysis showed that low expression of CXCL2 was associated with poor disease-specific survival time (DSS), relapse-free survival time (RFS) and overall disease survival (OS) in breast cancer patients. In addition, low expression of CXCL2 was associated with poor OS and RFS in patients with lymph node positive breast cancer. CXCL2 expression was positively correlated with the infiltration of B cells, CD4+T and CD8+T cells, neutrophils and dendritic cells (DCs) in BRCA, mainly in Luminal breast cancer. MiR-532-5p can directly regulate CXCL2 expression. High miR-532-5p expression is significantly correlated with HER2 negative, grade 2 and 3 and poor OS in patients with HER+ER- breast cancer. Conclusion: CXCL2 is closely related to the prognosis and immune infiltration level of breast cancer patients, it can be regulated by miR-532-5p.

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.

Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

2020 ◽  
Vol 20 (9) ◽  
pp. 681-688
Author(s):  
Nikolai V. Litviakov ◽  
Marina K. Ibragimova ◽  
Matvey M. Tsyganov ◽  
Artem V. Doroshenko ◽  
Eugeniy Y. Garbukov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal B ◽  
Cell Clones ◽  
Genetic Landscape ◽  
Intelligent Approach

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1918
Author(s):  
Mio Yamaguchi ◽  
Kiyoshi Takagi ◽  
Koki Narita ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Human Breast Carcinoma ◽  
Breast Cancer Patients ◽  
Breast Carcinomas ◽  
Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

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