scholarly journals Tumor Suppressor Effect of RBMS3 in Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Chunyang Wang ◽  
Yidan Wu ◽  
Yunqi Liu ◽  
Fushun Pan ◽  
Huijuan Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Rna Binding ◽  
Independent Prognostic Factor ◽  
Cancer Tissue ◽  
Nuclear Staining ◽  
Cancer Tissues ◽  
Er Status

Background: RBMS3 (RNA-binding motif, single-stranded-intervacting protein 3) acts as a tumor-suppressive gene in a number of human cancers, however, its role in breast cancer is not fully understood. This study aimed to investigate the expression and clinicopathological significance of RBMS3 in breast cancer. Methods: A total of 998 breast cancer tissue samples in The Cancer Genome Atlas (TCGA) database with survival outcomes were divided into high RBMS3 expression and low expression groups using the median as the cutoff. Clinicopathological characteristics and prognosis were compared between the 2 groups. Results: TCGA showed that RBMS3 mRNA was downregulated in breast cancer tissues, and RBMS3 downregulation was correlated with poor prognosis. Immunohistochemistry staining of 127 paraffin-embedded breast cancer tissues showed that RBMS3 protein was localized in the cytoplasm and nucleus; however, nuclear staining was present in 90.0% of normal breast tissues but only 28.3% of breast cancer tissues. Decreased RBMS3 protein expression was significantly correlated with estrogen receptor (ER)-negative status and death at final follow-up. Patients with lower RBMS3 protein expression had substantially shorter survival than those with higher RBMS3 expression. Univariate and multivariate analysis indicated that the combination of RBMS3 expression and ER status (a variable designated as “cofactor”) was an independent prognostic factor in patients with breast cancer (hazard ratio [HR] = 0.420, 95% confidence interval [CI]: 0.223-0.791, P = 0.007). Conclusion: RBMS3 downregulation was correlated with poor prognosis in breast cancer patients, and the combination of RBMS3 expression and ER status was an independent prognostic factor.

scholarly journals High BTBD7 Expression Positive Correlated with SLUG Predicted Poor Prognosis in Hormone Receptor Negative Breast Cancer

2020 ◽  
Author(s):  
Li Zi-xiong ◽  
Huang Ze-nan ◽  
Hui Luo ◽  
Yang Xiong-bin ◽  
Wang Yu-lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Hormone Receptor ◽  
Poor Prognosis ◽  
Benign Lesion ◽  
Cancer Tissue ◽  
Slug Expression ◽  
Her 2 ◽  
Mesenchymal Transformation

Abstract There is a poor prognosis of metastasis in hormone receptor negative breast cancer (HRNBC), including triple-negative breast cancer (TNBC) and HER-2 overexpression breast cancer. Recent studies have indicated that BTB/POZ domain-containing protein 7 (BTBD7) regulates SLUG which is a key EMT (epithelial-mesenchymal transformation)-associated protein. The role of BTBD7 in HRNBC, however, has not been identified. In this study, The Cancer Genome Atlas (TCGA) was used to identify BTBD7 mRNA expression in breast cancer. In addition, GO and Metascape were used to identify differentially expressed genes. Immunohistochemical staining were applied to determine the protein expression of Btbd7 and Slug in paraffin-embedded samples from 144 HRNBC patients and 30 benign lesion patients. In cancer tissue, 64.9% in TNBC and 70.0% in HER-2+ overexpression breast cancer of Btbd7 protein was expressed when compared with a 20% expression in benign lesion tissues. Increased Btbd7 expression was further associated with larger tumor volume and poor TNM stages in HRNBC patients. Higher BTBD7 mRNA expression level was associated with shorter disease free survival (DFS) time from TCGA data. Higher Btbd7 protein expression in HRNBC tissue was associated with shorter DFS and OS time. Btbd7 protein expression significantly correlated with Slug expression in HRNBC tissue. Combining Btbd7 and Slug expression had a high predictive value for 3-year and 5-year DFS. As such, the positive expression of Btbd7 may contribute towards the development of breast cancer, specifically HRNBC via the up-regulation of Slug expression. Btbd7 was concluded to be an important predictor for the diagnosis of HRNBC patients.

scholarly journals Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna E. M. Bastiaansen ◽  
A. Mieke Timmermans ◽  
Marcel Smid ◽  
Carolien H. M. van Deurzen ◽  
Esther S. P. Hulsenboom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Glutamate Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate ◽  
Metabotropic Glutamate Receptor 1 ◽  
Novel Target ◽  
Cancer Tissues

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jenny Stenström ◽  
Ingrid Hedenfalk ◽  
Catharina Hagerling
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Independent Prognostic Factor ◽  
Primary Tumors

Abstract Background Patients diagnosed with metastatic breast cancer have poor outcome with a median survival of approximately 2 years. While novel therapeutic options are urgently needed, the great majority of breast cancer research has focused on the primary tumor and less is known about metastatic breast cancer and the prognostic impact of the metastatic tumor microenvironment. Here we investigate the immune landscape in unique clinical material. We explore how the immune landscape changes with metastatic progression and elucidate the prognostic role of immune cells infiltrating primary tumors and corresponding lymph node and more importantly distant metastases. Methods Immunohistochemical staining was performed on human breast cancer tissue microarrays from primary tumors (n = 231), lymph node metastases (n = 129), and distant metastases (n = 43). Infiltration levels of T lymphocytes (CD3+), regulatory T lymphocytes (Tregs, FOXP3+), macrophages (CD68+), and neutrophils (NE+) were assessed in primary tumors. T lymphocytes and Tregs were further investigated in lymph node and distant metastases. Results T lymphocyte and Treg infiltration were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs in primary tumors correlated with proliferation (P = 0.007, P = 0.000) and estrogen receptor negativity (P = 0.046, P = 0.026). While both T lymphocyte and Treg infiltration had a negative correlation to luminal A subtype (P = 0.031, P = 0.000), only Treg infiltration correlated to luminal B (P = 0.034) and triple-negative subtype (P = 0.019). In primary tumors, infiltration of T lymphocytes was an independent prognostic factor for recurrence-free survival (HR = 1.77, CI = 1.01–3.13, P = 0.048), while Treg infiltration was an independent prognostic factor for breast cancer-specific survival (HR = 1.72, CI = 1.14–2.59, P = 0.01). Moreover, breast cancer patients with Treg infiltration in their distant metastases had poor post-recurrence survival (P = 0.039). Treg infiltration levels changed with metastatic tumor progression in 50% of the patients, but there was no significant trend toward neither lower nor higher infiltration. Conclusion Treg infiltration could have clinical applicability as a prognostic biomarker, deciphering metastatic breast cancer patients with worse prognosis, and accordingly, could be a suitable immunotherapeutic target for patients with metastatic breast cancer. Importantly, half of the patients had changes in Treg infiltration during the course of metastatic progression emphasizing the need to characterize the metastatic immune landscape.

Quantitative estimation of BRCA1 protein expression in breast cancer tissue using the method of flow cytometry

2016 ◽  
Vol 61 ◽  
pp. S183
Author(s):  
E. Shestakova ◽  
E. Dudko ◽  
A. Grishanina ◽  
V. Kirsanov ◽  
N. Vichljantzeva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Protein Expression ◽  
Quantitative Estimation ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Brca1 Protein

scholarly journals Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues

2012 ◽  
Vol 104 (23) ◽  
pp. 1815-1824 ◽  
Author(s):  
V. M. Neumeister ◽  
V. Anagnostou ◽  
S. Siddiqui ◽  
A. M. England ◽  
E. R. Zarrella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Quantitative Assessment ◽  
Ischemic Time ◽  
Cold Ischemic Time ◽  
Cancer Tissues

Detection of Isolated Tumor Cells in Bone Marrow Is an Independent Prognostic Factor in Breast Cancer

2003 ◽  
Vol 21 (18) ◽  
pp. 3469-3478 ◽  
Author(s):  
G. Wiedswang ◽  
E. Borgen ◽  
R. Kåresen ◽  
G. Kvalheim ◽  
J.M. Nesland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Vascular Invasion ◽  
Independent Prognostic Factor ◽  
Histologic Grade ◽  
Separate Analysis ◽  
Node Negative ◽  
Node Positive

Purpose: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. Patients and Methods: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. Results: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P = .011) and lymph node involvement (P < .001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P < .001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer–specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. Conclusion: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Circulating myeloid-derived suppressor cells: An independent prognostic factor in patients with breast cancer

2018 ◽  
Vol 234 (4) ◽  
pp. 3515-3525 ◽  
Author(s):  
Elham Safarzadeh ◽  
Shahryar Hashemzadeh ◽  
Pascal H.G. Duijf ◽  
Behzad Mansoori ◽  
Vahid Khaze ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Suppressor Cells ◽  
Independent Prognostic Factor ◽  
Myeloid Derived Suppressor Cells
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