scholarly journals Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5769
Author(s):  
Nazia Riaz ◽  
Samantha Burugu ◽  
Angela S. Cheng ◽  
Samuel C. Y. Leung ◽  
Dongxia Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Prognostic Significance ◽  
Outcome Data ◽  
Carcinoma Cells ◽  
Cancer Tissue ◽  
Immune Biomarkers ◽  
Grade 3 ◽  
Positive Correlations ◽  
Aggressive Breast Cancer

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of CSF1R mRNA with immune infiltrates and prognosis. Following a prespecified training–validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between CSF1R mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.

scholarly journals Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Nobili ◽  
Antonella Mannini ◽  
Astrid Parenti ◽  
Chiara Raggi ◽  
Andrea Lapucci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Biology ◽  
Cancer Cell Line ◽  
Cancer Tissue ◽  
Endoplasmic Reticulum Membrane ◽  
Mcf 7

AbstractInvasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

scholarly journals Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

2019 ◽  
Vol 121 (9) ◽  
pp. 776-785 ◽  
Author(s):  
Chitra Joseph ◽  
Sara Al-Izzi ◽  
Mansour Alsaleem ◽  
Sasagu Kurozumi ◽  
Michael S Toss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Distant Metastasis ◽  
Prognostic Significance ◽  
Retinoid X Receptor ◽  
Cancer Tissue ◽  
Lower Grade ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Er Positive

Abstract Background Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

scholarly journals Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Karama Asleh ◽  
Nazia Riaz ◽  
Angela S. Cheng ◽  
Dongxia Gao ◽  
Samuel C. Y. Leung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Immune Checkpoint Blockade ◽  
Intrinsic Subtype ◽  
Cancer Tissue ◽  
Immune Biomarkers ◽  
Basal Like Breast Cancer ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

AbstractPrecise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n = 300; validation set: n = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes. Within the basal-like subtype, tumors with low DNA-PKcs and high tumor-infiltrating lymphocytes displayed the most favourable survival. DNA-PKcs expression by immunohistochemistry identified estrogen receptor-positive cases with a basal-like gene expression subtype. Non-silent mutations in PRKDC were significantly associated with poor outcomes. Integrating DNA-PKcs expression with validated immune biomarkers could guide patient selection for DNA-PKcs targeting strategies, DNA-damaging agents, and their combination with an immune-checkpoint blockade.

scholarly journals S-nitrosylated and non-nitrosylated COX2 have differential expression and distinct subcellular localization in normal and breast cancer tissue

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Sonali Jindal ◽  
Nathan D. Pennock ◽  
Alex Klug ◽  
Jayasri Narasimhan ◽  
Andrea Calhoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Biochemical Characterization ◽  
Disease Risk ◽  
High Specificity ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Early Onset Breast Cancer ◽  
And Function ◽  
Cox2 Expression

AbstractImmunohistochemical (IHC) staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form, and CX229 and CX294 recognizing non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early-onset breast cancer had increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 IHC studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.

scholarly journals Cytokeratin 7-Negative and GATA Binding Protein 3-Negative Breast Cancers: Clinicopathological Features and Prognostic Significance

2019 ◽  
Author(s):  
Shaolei Lu ◽  
Evgeny Yakirevich ◽  
Li Juan Wang ◽  
Murray B Resnick ◽  
Yihong Wang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Molecular Subtype ◽  
Binding Protein ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Cytokeratin 7 ◽  
Gata3 Expression ◽  
Grade 3

Abstract Background: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. Methods: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival. Results: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P=0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2 % of Grade 1 cases were GATA3 negative (P<0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor. Conclusions: More CK7 negative and GATA3 negative tumors were seen in breast cancer of high histologic grade. GATA3 expression was associated with ER status. Lack of CK7 and GATA3 expression in Grade 3 breast cancer was not associated with patient outcome.

scholarly journals Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signaling pathway in breast cancer

2020 ◽  
Author(s):  
Yizi Cong ◽  
Yuxin Cui ◽  
Shiguang Zhu ◽  
Jianqiao Cao ◽  
Guangdong Qiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tight Junction ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Prognostic Significance ◽  
Gene Expression Level ◽  
Expression Level ◽  
Cancer Tissue ◽  
Junction Molecules

Abstract Background: T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, but its exact role in breast cancer has not been fully elucidated. Methods: The gene expression level of Tim-3 in breast cancer and its prognostic significance were analysed. In vitro functions and associated mechanisms were then explored through establishing Tim-3 overexpressing breast cancer cells. Results: The gene expression level of Tim-3 was significantly higher (p<0.001) in breast cancer tissue compared to normal tissue following pooled analysis of the TCGA database. Tim-3 was a prognosis indicator in breast cancer patients as shown by KM-plotter (RFS: p=0.004; OS: p=0.099). Overexpression of the Tim-3 in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells including proliferation, migration, invasion, tight junction deterioration and tumour-associated tubal formation. Furthermore, Tim-3 enhanced cellular resistance to paclitaxel. Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway, and mediating gene regulation (upregulating CCND1, C-Myc, MMP1, TWIST, VEGF while downregulating E-cadherin). Additionally, Tim-3 downregulated tight junction molecules: ZO-2, ZO-1 and Occludin, which might further facilitate the tumour progression. Conclusions: Tim-3 plays a tumour-promoting role in breast cancer, suggesting that targeting Tim-3 may acquire a clinical benefit in antitumor therapy. Keywords: breast cancer, Tim-3, tight junction, chemoresistance, aggressiveness.

scholarly journals Expression of Mesothelial Marker Calretinin in Breast Cancer

2019 ◽  
Vol 4 (01) ◽  
Author(s):  
Dr. Kalathingal Kamarunisha Aboobacker ◽  
Dr. Prema Saldanha
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Calcium Binding ◽  
Invasive Carcinoma ◽  
Prognostic Significance ◽  
Immunohistochemical Expression ◽  
Node Negative ◽  
Mastectomy Specimen ◽  
Grade 3

Calretinin (CR) is a calcium binding protein of calmodulin superfamily, a widely used marker for mesothelial differentiation. It is also found to be expressed in breast carcinoma. Breast carcinoma is the leading cause of cancer death in women and despite new approaches and advances, it is still difficult to predict the behaviour of the tumour and its prognosis. So there is a need and struggle to identify new markers for prognosis of breast cancer. The study is aimed at evaluating the frequency of Calretinin expression in breast carcinoma and assessing the characteristics of Calretinin positive tumours. Thirty mastectomy specimen of invasive breast carcinoma were analysed histopathologically and for immunohistochemical expression of ER, PR, HER2/neu and Calretinin. In this study 93.33% (28 cases) were of invasive carcinoma, NST and 6.67% were of other subtypes. Patients less than 40 years of age showed low CR expression and patients over 40 showed high CR expression (p = 0.22). Grade 3 tumours showed high CR, grades 1 and 2 showed low CR expression. Lymph node positive cases showed high CR and lymph node negative cases showed low CR. Tumours less than 5cms in size show low CR expression and those over 5cms showed high CR expression (p = 0.38). Negative ER, PR and HER2/neu showed high CR expression. CR expression was high in 54.5% of basal-like subtype and 66.7% of HER2-enriched.CR expression was low in 50% of luminal cases. High Calretinin expression was seen in grade 3, HER2-enriched and basal-like subtypes of breast cancer which may be of considerable prognostic significance.

scholarly journals LINC01087 indicates a poor prognosis of glioma patients with preoperative MRI

2021 ◽  
Author(s):  
Wangsheng Chen ◽  
Fei Wang ◽  
Jianhua Zhang ◽  
Changqing Li ◽  
Lan Hong
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Glioma Cells ◽  
Cancer Tissue ◽  
Non Coding Rna ◽  
Mri Diagnosis ◽  
The Relationship ◽  
U251 Cells

AbstractLong intergenic non-coding RNA 01,087 (LINC01087) has been concerned as an oncogene in breast cancer, while its mechanism in glioma has been little surveyed. Thus, we searched the prognostic value and functional action of LINC01087 in glioma. Glioma patients after preoperative MRI diagnosis were enrolled, and LINC01087, microRNA (miR)-1277-5p, and alkaline ceramidase 3 (ACER3) levels were tested in glioma cancer tissue. The correlation between LINC01087 expression and the survival of patients were analyzed. LINC01087, miR-1277-5p, and ACER3 levels in U251 cells were altered via transfection, and cell malignant phenotypes were monitored. The relationship between miR-1277-5p and LINC01087 or ACER3 was detected. The LINC01087 and ACER3 expression was in up-regulation and the miR-1277-5p expression was in down-regulation in clinical glioma samples. High expression of LINC01087 was associated with poor prognosis of glioma patients with preoperative MRI. LINC01087 silencing restrained tumor malignancy in glioma cells. Mechanistically, LINC01087 directly interacted with miR-1277-5p. ACER3 was a known target of miR-1277-5p. Moreover, rescue assays reveal that miR-1277-5p overexpression (or ACER3 overexpression) reversed the effects of LINC01087 upregulation (or miR-1277-5p upregulation) on glioma cells. LINC01087 has prognostic significance in glioma and silencing LINC01087 deters glioma development through elevating miR-1277-5p to reduce ACER3 expression.

scholarly journals CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan-ke Liang ◽  
Ze-kun- Deng ◽  
Mu-tong Chen ◽  
Si-qi Qiu ◽  
Ying-sheng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Immune Cell ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Immune Checkpoint Blockade ◽  
Cancer Tissue ◽  
Related Factors ◽  
Immune Infiltration ◽  
Potential Biomarker

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer.

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