scholarly journals Altered Sirtuin 7 Expression is Associated with Early Stage Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S23156 ◽  
Author(s):  
Ahmad Aljada ◽  
Ayman M. Saleh ◽  
Moath Alkathiri ◽  
Heba Bani Shamsa ◽  
Ahmad Al-Bawab ◽  
...  

Background To evaluate sirtuin-7 (SirT7) mRNA expression status in breast cancer patients with different metastatic stages and survey SirT7 mRNA expression status in eight different types of cancer. Methods The expression of SirT7 in the commercially available TissueScan qPCR Breast Cancer Disease cDNA arrays containing 16 normal, 23 Stage I, 36 IIA, 22 IIB, 8 IIIA, 23 IIIA, 6 IIIB, 13 IIIC, and 5 IV were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Similar analysis was performed in TissueScan qPCR Cancer Survey cDNA array, which includes breast, colon, kidney, liver, lung, ovarian, prostate, and thyroid specimens. Results The mRNA expression levels of SirT7 were significantly higher in breast cancer samples compared to normal breast specimens ( P < 0.001). Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of SirT7 mRNA in CS-I, CS-II, and CS-III when compared to normal breast tissue ( P < 0.05). Notably, SirT7 mRNA levels were higher in CS-I, CS-IIA, CS-IIB, and CS-IIIA ( P < 0.05). Additionally, there were significantly lower SirT7 mRNA levels in thyroid carcinoma when compared to their corresponding normal tissue ( P < 0.05). Conclusions Our results indicate an increase in the mRNA expression level of SirT7 in breast cancer, particularly in CS-I, CS-IIA, CS-IIB, and CS-IIIA. The relationship of altered SirT7 with breast cancer progression and patient survival should be prospectively explored in future studies.

Author(s):  
Pan Ding ◽  
XiaoMing Du ◽  
LiHui Wan ◽  
Xueke Zhao ◽  
DeRui Zhang ◽  
...  

Background: Breast cancer is more likely to metastasize to the bone. Previous researches have revealed that vitamin D receptor (VDR) contributes to breast cancer progression and bone metastasis in mouse and human breast cells, and Hairless (Hr) protein interacts with VDR in the mammalian hair cycle. This study aimed to explore the expression of VDR/Hr in breast cancer, and the correlation between VDR/Hr and prognosis, bone metastasis, and metastasis-related prognosis. Methods: The expression of VDR and Hr was performed on 119 breast cancer tissues and corresponding normal breast tissue from each of the breast cancer samples by Immunohistochemistry (IHC) staining, and the databases were supplemented as well. Results: The expression of VDR protein was significantly decreased in breast cancer patients (p < 0.05), inversely, the UALCAN (p = 0.000) and GEPIA (p > 0.05) databases showed VDR mRNA expression tended to be higher in tumor tissues. Hr protein was expressed at low level within breast cancer specimens (p < 0.05), which was in agreement with the level of Hr mRNA in the UALCAN (p = 0.005) and GEPIA (p > 0.05). The protein levels of VDR and Hr were positively correlated (p > 0.05), while the mRNA levels suggested a closely relationship in the GEPIA (p < 0.05). Low expression of Hr protein displayed a tendency for longer overall survival (OS) and recurrence-free survival (RFS), and its mRNA data also revealed the same trend in the KM dataset (both p > 0.05). Whereas, VDR protein and mRNA low expression had markedly shorter OS and RFS (both p < 0.05). The down-regulation of VDR protein was significantly associated with advanced stage (p < 0.05). Low VDR protein was an independent risk factor for poor prognosis (p < 0.05) and was negatively correlated with bone metastasis (p < 0.05). VDR protein and mRNA levels were both down-regulated in breast cancer with bone metastasis (both p < 0.05). The area under ROC curve (AUC) for VDR protein expression to identify patients with bone metastasis was 0.661 (p < 0.05) and the AUC for VDR level to predict 1-year 3-year, 5-year OS was 0.621, 0.664, and 0.805 in patients with bone metastasis, respectively (p < 0.05). VDR low expression accelerated bone metastasis and metastasis-related poor survival (both p < 0.05). Conclusion: VDR expression is a notably prognostic factor in primary breast cancer patients for predicting bone metastases and unfavorable clinical outcome.


2019 ◽  
Vol 79 (02) ◽  
pp. 184-188 ◽  
Author(s):  
Carsten Gründker ◽  
Matthias Läsche ◽  
Johanna Hellinger ◽  
Günter Emons

AbstractTumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21075-21075
Author(s):  
C. F. Singer ◽  
D. Gschwantler-Kaulich ◽  
A. Fink-Retter ◽  
G. Hudelist ◽  
C. Haas ◽  
...  

21075 Background: Breast cancer is chatacterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumoral fibroblasts display unique phenotypical properties, it is unclear whether they also represent are a specific subpopulation. Materials and Methods: Stromal fibroblasts deriving from malignant tissue of 10 women with invasive breast cancer, and from normal breast tissue of 10 women with benign breast disorders, were subjected to differential complementary DNA Microarray Analysis by using a 2400 gene cDNA array. Gene expression results were validated by real-time PCR and by immunohistochemistry. Results: In a cDNA Array that allows to analyze the differential gene expression of more than 2400 genes, the mRNA expression of 135 genes were increased more than 2 fold in fibroblasts from malignant breast tumors. The majority of these genes encode tumor-promoting cytokines, transcription factors and cell-matrix associated proteins. The mRNA expression of 110 genes decreased to less than 0.5 fold. The remaining 2155 genes were not significantly altered. Immunohistochemistry for selected proteins performed on biopsies from breast cancer and normal breast tissues confirmed the clinical relevance of our findings. Conclusion: Breast cancer-derived stromal fibroblasts show a distinctive gene expression pattern that differentiates them from normal breast stroma. Our observation of increased expression of tumor promotion-associated genes even in the absence of adjacent malignant epithelium suggests that tumor stroma is comprised of a fibroblastic subpopulation that provides for a microenvironment which supports tumor growth and invasion. No significant financial relationships to disclose.


2018 ◽  
Vol 7 (10) ◽  
pp. 5066-5082 ◽  
Author(s):  
Marinos Tsiatas ◽  
Konstantine T. Kalogeras ◽  
Kyriaki Manousou ◽  
Ralph M. Wirtz ◽  
Helen Gogas ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shreeya Kotecha ◽  
Marie N. Lebot ◽  
Bhudsaban Sukkarn ◽  
Graham Ball ◽  
Paul M. Moseley ◽  
...  

AbstractDopamine and cAMP regulated phosphoprotein 32 kDa (DARPP-32) also known as phosphoprotein phosphatase-1 regulatory subunit 1B and encoded by the PPP1R1B gene is an inhibitor of protein phosphatase-1 and protein kinase A. DARPP-32 is expressed in a wide range of epithelial cells and some solid tumours; however, its role in breast cancer is only partially defined. DARPP-32 expression was determined using immunohistochemistry in two independent cohorts of early stage invasive breast cancer patients (discovery n = 1352; validation n = 1655), and 112 HER2 positive breast cancer patients treated with trastuzumab and adjuvant chemotherapy. PPP1R1B mRNA expression was assessed in the METABRIC cohort (n = 1980), using artificial neural network analysis to identify associated genes. In the discovery cohort, low nuclear expression of DARPP-32 was significantly associated with shorter survival (P = 0.041), which was independent of other prognostic variables (P = 0.019). In the validation cohort, low cytoplasmic and nuclear expression was significantly associated with shorter survival (both P = 0.002), with cytoplasmic expression independent of other prognostic variables (P = 0.023). Stronger associations with survival in oestrogen receptor (ER) positive disease were observed. In patients treated with trastuzumab, low nuclear expression was significantly associated with adverse progression-free survival (P = 0.031). In the METABRIC cohort, low PPP1R1B expression was associated with shortened survival of ER positive patients. Expression of CDC42 and GRB7, amongst others, were associated with PPP1R1B expression. This data suggests a role for DARPP-32 as a prognostic marker with clinical utility in breast cancer.


2010 ◽  
Vol 17 (1) ◽  
pp. 215-230 ◽  
Author(s):  
Ton van Agthoven ◽  
Anieta M Sieuwerts ◽  
Danielle Meijer ◽  
Marion E Meijer-van Gelder ◽  
Thecla L A van Agthoven ◽  
...  

Although endocrine treatment of breast cancer is effective and common practice, in advanced disease the development of resistance is nearly inevitable. To get more insight into individual genes that account for resistance against hormonal agents, we have executed functional genetic screens and subsequently evaluated the clinical relevance of several identified genes with respect to tumor aggressiveness and tamoxifen resistance in estrogen receptor-positive patients. Estrogen-dependent human breast cancer cells were transduced with different retroviral cDNA expression libraries and subjected to selective cultures with various anti-estrogens. From a total of 264 resistant cell clones, 132 different genes were recovered by PCR. By applying stringent selection criteria, we identified 15 breast cancer anti-estrogen resistance (BCAR) genes individually yielding resistance. BCAR genes were recovered with differential frequencies for the diverse culture conditions and anti-estrogen drugs. Analysis of the relation of BCAR genes (EIF1, FBXL10, HRAS, NRG1, PDGFRA, PDGFRB, RAD21, and RAF1) with tamoxifen treatment in patients with advanced disease showed significant association with clinical benefit and progression-free survival for EIF1 and PDGFRA mRNA levels. Furthermore, PDGFRA and HRAS mRNA levels were significantly associated with tumor aggressiveness in lymph node-negative patients who had not received adjuvant systemic therapy. In conclusion, our functional genetic screens showed that BCAR genes differ in their ability to confer resistance towards distinct anti-estrogens. Based on the clinical relevance of several BCAR genes, further studies are warranted to characterize the underlying mechanisms, which may ultimately lead to the development of novel treatments and more individualized management of breast cancer patients.


2021 ◽  
Vol 7 (1) ◽  
pp. 46
Author(s):  
Dinna Rakhmina ◽  
Sofia Mubarika Haryana ◽  
Teguh Aryandono

MiR-21 has been linked to tumorigenesis, development, and metastasis in tumor pathogenesis. All human cancers, including breast cancer, have increased expression of MiR-21, which is the only miRNA that has increased expression. PTEN expression was found to be reduced in the majority of solid tumors, including breast cancer. Since lymph node metastatic factors, estrogen receptor status, tumor grade, and tumor node metastasis (TNM) all decreased PTEN expression, the PTEN expression profile may be a very useful prognostic marker in breast cancer. PTEN inhibits PIP3 (phosphatidylinositol 3,4,5-triphosphate) activity by having protein phosphatase and lipid phosphatase activity that is the polar opposite of PI3K (Phosphatidyl Inositol 3-Kinase). The aim of this research was to see how often miR-21 and mRNA PTEN were expressed at different stages of breast cancer and whether they could be used as prognostic markers. This type of research is an observational study with a cross-sectional design. The sample size of 43 people came from breast cancer patients. Analysis of miR-21 expression and mRNA PTEN using Real-Time qPCR. The results showed that miR-21 expression increased 1.32 times at an advanced stage compared to an early stage, while mRNA PTEN expression decreased 1.33 fold at an advanced stage compared to an early stage. According to the findings, miR-21 expression in the blood plasma of breast cancer patients was upregulated at an advanced stage compared to an early stage and downregulated mRNA PTEN expression. MiR-21 which is increased at an advanced stage has the potential to be a poor prognostic marker at the stage of breast cancer. The change in miR-21 expression can be a good candidate as a molecular prognostic marker and for future research the role of miR-21 in breast cancer progression will further enrich the scientific repertoire, especially in the health and clinical fields.


2021 ◽  
Author(s):  
Duo You ◽  
Danfeng Du ◽  
Xinmin Li ◽  
Xun Hu

Abstract Purpose: While malic enzymes 1 (ME1) was correlated with breast cancer progression and prognosis, the association of ME3 (a homologue of ME1) with breast cancer is not known. The aim of this study is to explore the potential of ME3 as a biomarker in breast cancer carcinogenesis and prognosis.Methods: A total of 107 patients confirmed with breast cancer were enrolled. The ME3 expression was evaluated by IHC and correlated with clinicopathological indicators.Results: The ME3 positive immunostaining rate was higher in normal breast tissues and decreased stepwise from normal (97.60%) to usual ductal hyperplasia (91.1%), atypical ductal hyperplasia (64.2%), carcinoma in situ (62.5%) and invasive carcinoma (45.5%). Similarly, the decreasing tendency was observed for ME3 positive immunostaining rate from Tis (75.0%) through T1 (62.5%) and T2 (37.5%) to T3 (33.3%) and from stag 0 (75.0%) through I (72.0%), II (44.4%) to III (24.1%). ME3 expression was related with negative lymph node metastasis. Patients with positive expression of ME3 had better outcome. By incorporating ME3 into tumor TNM staging, the area under receiver operating characteristic curve for the 5-year survival was increased from 84.0% to 87.5%. Conclusions: ME3 may be a promising biomarker for better prognosis for breast cancer patients.


2000 ◽  
Vol 15 (3) ◽  
pp. 210-214 ◽  
Author(s):  
F. Spyratos ◽  
C. Andrieu ◽  
D. Vidaud ◽  
M. Briffod ◽  
M. Vidaud ◽  
...  

To elucidate the role of CCND1 alterations in sporadic breast cancer we investigated the possible link between CCND1 mRNA levels versus estrogen-receptor (ER) status and a proliferation marker, S-phase fraction (SPF), measured by flow cytometry. CCND1 expression was quantified by means of real-time quantitative RT-PCR in a well-characterized series of 33 primary breast cancer patients. Eighteen tumors (54.5%) showed CCND1 overexpression ranging from 3.3 to 29.5 times the level observed in normal breast tissue. Seventeen (94.4%) of the 18 cases with CCND1 overexpression were ER-positive compared to seven (46.7%) of the 15 cases with normal CCND1 expression (p=0.0074). CCND1 overexpression was independent of SPF and DNA-ploidy status. These data suggest that the CCND1 gene does not act as an oncogene responsible for more rapid cell proliferation in breast cancer, but could be involved in the regulation of hormone sensitivity associated with ER.


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