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 ◽  
...  

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.

2021 ◽  
Author(s):  
Li Zi-xiong ◽  
Huang Ze-nan ◽  
Hui Luo ◽  
Yang Xiong-bin ◽  
Wang Yu-lin ◽  
...  

Abstract BACKGROUND: Hormone receptor-negative breast cancer (HRNBC), including triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER-2) overexpressing breast cancer, is prone to metastasis and has a poor prognosis. BTB/POZ domain-containing protein 7 (Btbd7) is considered to regulate Slug and the epithelial-mesenchymal transition (EMT) process. However, the role of Btbd7 in HRNBC is unclear. This study aimed to investigate the localization and function of Btbd7 in HRNBC as well as its relationship with Slug and the EMT process.METHODS: Bioinformatics analysis was performed to evaluate the effect of the BTBD7 and SLUG genes expression on the prognosis in HRNBC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify differentially expressed genes (DEGs) and possible mechanism in breast cancer. Expression of Btbd7 and Slug in 144 HRNBC and 30 benign lesion tissues obtained from the patients was evaluated using immunohistochemistry and immunofluorescence staining. MDA-MB-231 cells were transfected with BTBD7 siRNA and the expression levels of Btbd7, Slug, and key EMT proteins were analyzed. CCK-8 and cell invasion assays were performed to evaluate cell proliferation and invasion in response to BTBD7 silencing.RESULTS: The total positive rate of Btbd7 expression in HRNBC tumor tissue was 66.7% (96/144), which was higher than that in normal adjacent tissue (NAT) (52.1% 75/144 P=0.001) and benign breast lesion tissues (20%, 6/30 P<0.001). TCGA and immunohistochemistry staining both indicated that higher Btbd7 and Slug expression in HRNBC was associated with poor clinicopathologic features and prognosis. Co-expression of Slug and Btbd7 proteins could be found in HRNBC tissue and MDA-MA-231 cells. BTBD7 silencing significantly up-regulated the epithelial marker E-cadherin (P<0.05), down-regulated the mesenchymal markers α-SMA and Slug (P<0.05), and suppressed the proliferation and invasion abilities of cells. GO and KEGG analyses based on 322 DEGs showed that BTBD7 may be associated with generic transcription in breast cancer.CONCLUSION: Higher expression of BTBD7 was a poor prognostic factor in HRNBC patients and BTBD7 silencing inhibited EMT through regulation of Slug expression. BTBD7 might act as a potential molecular target for gene therapy in HRNBC patients.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 413-413
Author(s):  
E. J. Jordan ◽  
M. P. Farrell ◽  
R. M. Clarke ◽  
M. R. Kell ◽  
J. A. McCaffrey ◽  
...  

413 Background: Breast cancer is not a recognised malignant manifestation of Lynch Syndrome which includes colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland, and a genotype phenotype correlation was investigated. One kindred was omitted due to the presence of a biallelic MMR and BRCA1 mutation. The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in 16 pedigrees was as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Six MSH2 mutations and 1 MSH6 mutation were identified in the 7 Lynch syndrome kindreds. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. Final results of immunohistochemistry for mismatch repair protein expression on breast cancer samples are pending and will be reported at the meeting. One breast cancer has been tested to date and demonstrated loss of MSH2 protein expression in an individual carrying an MSH2 mutation. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna Göthlin Eremo ◽  
Kajsa Lagergren ◽  
Lana Othman ◽  
Scott Montgomery ◽  
Göran Andersson ◽  
...  

AbstractBreast cancer patients treated with tamoxifen may experience recurrence due to endocrine resistance, which highlights the need for additional predictive and prognostic biomarkers. The glyco-phosphoprotein osteopontin (OPN), encoded by the SPP1 gene, has previously shown to be associated with poor prognosis in breast cancer. However, studies on the predictive value of OPN are inconclusive. In the present study, we evaluated tissue SPP1 mRNA and OPN protein expression as markers of recurrence in estrogen receptor- positive (ER+) breast cancer tissue. Tamoxifen- treated patients with recurrence or non-recurrence were selected using a matched case-control design. SPP1 mRNA expression was analysed using qPCR (n = 100) and OPN protein by immunohistochemistry (n = 116) using different antibodies. Odds ratios were estimated with conditional logistic regression. The SPP1 expression increased the risk of recurrence with an odds ratio (OR) of 2.50 (95% confidence interval [CI]; 1.30–4.82), after adjustment for tumour grade, HER 2 status and other treatments to OR 3.62 (95% CI; 1.45–9.07). However, OPN protein expression was not associated with risk of recurrence or with SPP1-gene expression, suggesting SPP1 mRNA a stronger prognostic marker candidate compared to tumor tissue OPN protein.


2021 ◽  
Author(s):  
Yasuaki Uemoto ◽  
Eriko Katsuta ◽  
Naoto Kondo ◽  
Yumi Wanifuchi-Endo ◽  
Takashi Fujita ◽  
...  

Abstract HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts using mRNA and protein expression, and bioinformatics. We examined the prognostic significance of HECTD1 by multivariate analysis. HECTD1 mRNA expression (HECTD1 expression) was lower in breast cancer compared with adjacent normal tissues. HECTD1 expression levels also differed among breast cancer subtypes. Decreased HECTD1 expression was significantly associated with aggressive tumour characteristics, including large tumour size and high histological grade. HECTD1 expression was inversely associated with mitochondrial cellular respiratory function and reactive oxygen species in breast cancer tissues. Multivariate analysis identified low HECTD1 mRNA expression level as an independent risk factor for disease-free (P = 0.009) and overall (P = 0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with mRNA expression and prognosis. HECTD1 mRNA expression is a candidate prognostic biomarker in breast cancer. The poor prognosis of patients with low HECTD1 mRNA expression may be associated with increased mitochondrial respiratory function.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Chunyang Wang ◽  
Yidan Wu ◽  
Yunqi Liu ◽  
Fushun Pan ◽  
Huijuan Zeng ◽  
...  

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.


2004 ◽  
Vol 84 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Christian Rudlowski ◽  
Nicolaus Friedrichs ◽  
Andree Faridi ◽  
Lazlo Füzesi ◽  
Roland Moll ◽  
...  

2016 ◽  
Vol 61 ◽  
pp. S183
Author(s):  
E. Shestakova ◽  
E. Dudko ◽  
A. Grishanina ◽  
V. Kirsanov ◽  
N. Vichljantzeva ◽  
...  

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Atef Youssef Riyad ◽  
Dalia Abdelghany Elkhodary ◽  
Wesam Reda Farag Elghamry ◽  
Islam Abdelrahman Kamel Mohamed Zaki

Abstract Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.


2013 ◽  
Vol 47 (1) ◽  
pp. 57-62
Author(s):  
Alessandro Tuzi ◽  
Davide Lombardi ◽  
Diana Crivellari ◽  
Loredana Militello ◽  
Tiziana Perin ◽  
...  

Abstract Background. We report on the activity of the combination of epirubicin and docetaxel given in neoadjuvant setting for 4 and 8 cycles respectively in 2 successive series of patients with large operable or locally advanced, hormone receptor positive, HER-2 negative breast cancer. Patients and methods. Patients were treated from 2002 to 2006 with epirubicin 90 mg/m2 and docetaxel 75 mg/ m2 intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery (Series I - 13 patients), and from 2006 to 2010 with the same regimen administered for 8 cycles preoperatively (Series II - 37 patients), plus hormonal therapy for 5 years and radiation therapy if indicated. All Series I and 32 Series II patients were able to complete the preoperative chemotherapy. Results. A complete response was found in 1 patient from Series I and 13 patients from Series II and the partial remission in 10 patients from Series I and 21 patients from Series II. Two Series I and 3 Series II patients did not respond clinically. Response rate (Series I/Series II) was 84/92%. All 50 patients underwent surgery. In Series I patients, 3 pCR occurred in the breast and the axilla was histologically negative in 2 cases. No evidence of disease both in the breast and in the axilla was achieved in 7.6% (1/13) of patients. In Series II patients, 8 pCR occurred in the breast and axilla was histologically negative in 15 patients. No evidence of disease both in the breast and in the axilla occurred in 10.8% (4/37) of patients. G3-G4 toxicity included myelosuppression in 3 patients from Series I and all patients from Series II, and mucositis in 1 patient from Series I and 4 patients from series II. No other G3-4 toxicities or toxic deaths occurred. Five-year progression free survival was 38% and 90% in Series I and Series II patients respectively. Conclusions. The incidence of pathologic complete remissions was lower in our patient population, compared to reported data. A longer duration of the preoperative treatment might be associated with a longer progression-free survival.


Sign in / Sign up

Export Citation Format

Share Document