scholarly journals Circulating miR-99a-5p Expression in Plasma: A Potential Biomarker for Early Diagnosis of Breast Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7427
Author(s):  
Iris Garrido-Cano ◽  
Vera Constâncio ◽  
Anna Adam-Artigues ◽  
Ana Lameirinhas ◽  
Soraya Simón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Cancer Tissues ◽  
Breast Tissues

MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analysed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. MiR-99a-5p expression levels were determined by quantitative real-time PCR in three independent cohorts of patients: (I) Discovery cohort: breast cancer tissues (n = 103) and healthy breast tissues (n = 26); (II) Testing cohort: plasma samples from 105 patients and 98 healthy donors; (III) Validation cohort: plasma samples from 89 patients and 85 healthy donors. Our results demonstrated that miR-99a-5p was significantly downregulated in breast cancer tissues compared to healthy breast tissues. Conversely, miR-99a-5p levels were significantly higher in breast cancer patients than in healthy controls in plasma samples from both testing and validation cohorts, and ROC curve analysis revealed that miR-99a-5p has good diagnostic potential even to detect early breast cancer. In conclusion, miR-99a-5p’s deregulated expression distinguished healthy patients from breast cancer patients in two different types of samples (tissues and plasma). Interestingly, expression levels in plasma were significantly lower in healthy controls than in early-stage breast cancer patients. Our findings suggest circulating miR-99a-5p as a novel promising non-invasive biomarker for breast cancer detection.

scholarly journals The expression and clinical significance of GADD45A in breast cancer patients

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5344 ◽  
Author(s):  
Junnan Wang ◽  
Yiran Wang ◽  
Fei Long ◽  
Fengshang Yan ◽  
Ning Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Expression Levels ◽  
Cancer Tissues

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.

scholarly journals Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Breast Care ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Kheirollah Yari ◽  
Zohreh Rahimi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Retinoic Acid Receptor ◽  
Methylation Status ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Retinoic Acid Receptor Beta ◽  
Cancer Tissues ◽  
Breast Tissues ◽  
Receptor Beta

Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.

scholarly journals Secreted Frizzled-Related Protein 2 Is Associated with Disease Progression and Poor Prognosis in Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chumei Huang ◽  
Zhuangjian Ye ◽  
Jianxin Wan ◽  
Jianbo Liang ◽  
Min Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Cancer Drug ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Related Protein ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Potential Biomarker

Purpose. Secreted frizzled-related protein 2 (sFRP2) is a secreted protein associated with cancer drug resistance and metastasis. However, few studies have reported serum sFRP2 levels in breast cancer. We evaluated serum sFRP2 as a potential biomarker for breast cancer. Methods. Serum sFRP2 concentrations were detected in 274 breast cancer patients along with 147 normal healthy controls by enzyme-linked immunosorbent assay (ELISA). Diagnostic significance was evaluated by area under the curve (AUC) analysis and the Youden index. Prognostic significance was determined by Kaplan-Meier survival method and univariate and multivariate Cox proportional hazard regression model analyses. Results. Serum sFRP2 was elevated in breast cancer patients compared to normal healthy controls (P<0.001). The sensitivity of sFRP2 in diagnosing breast cancer was 76.9% at a specificity of 76.6%. Elevated serum sFRP2 levels are associated with primary tumor size, TNM stage, and lymph node metastases. The Kaplan-Meier curves showed a significant association of serum sFRP2 with progression-free survival. The multivariate Cox analysis confirmed that high serum sFRP2 was an independent prognostic factor for poor prognosis (HR=3.89, 95% CI=1.95-7.68, P=0.001). Conclusions. In conclusion, serum sFRP2 may serve as a potential biomarker for breast cancer diagnosis and prognostic evaluation.

scholarly journals Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients

2016 ◽  
Vol 62 (7) ◽  
pp. 1002-1011 ◽  
Author(s):  
Athina Markou ◽  
Martha Zavridou ◽  
Ioanna Sourvinou ◽  
George Yousef ◽  
Sofia Kounelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Breast Tumors ◽  
Breast Cancer Patients ◽  
Healthy Individuals ◽  
Primary Tumors ◽  
Expression Levels ◽  
Breast Tissues

Abstract BACKGROUND Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors. METHODS Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available. RESULTS In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P &lt; 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR-210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231–7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals. CONCLUSIONS Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals.

Comprehensive Analysis of the Expression and Prognostic Significance of THBSs in Breast Cancer

2021 ◽  
Author(s):  
Jun Wang ◽  
Xuebing Zhan ◽  
Qian Luo ◽  
Yunshu Kuang ◽  
Xiao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Protein Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Expression Levels ◽  
Cancer Tissues ◽  
Mrna Expression Levels

Abstract Background: Breast cancer is one of the most common tumors for women worldwide. Thrombospondins (THBSs) are reported to play important roles in various cellular processes and are involved in the occurrence and development of human cancers. However, the expression and prognostic value of THBSs family in breast cancer remain unclear.Methods: In this study, we examined the genes and protein expression levels of THBSs and their prognostic value by synthesizing several mainstream databases, including Oncomine, Human Protein Atlas (HPA), UALCAN, and KM Plotter. We also analyzed THBS interaction networks, genetic alterations, functional enrichment, and drug sensitivity with several publicly accessible databases, including GEPIA, GeneMANIA, STRING, cBioPortal, Metascape and NCI-60 database.Results: The results showed that the mRNA expression levels of THBS1, THBS2, THBS3, and THBS5 in breast cancer tissues were significantly higher than in normal tissues. The mRNA expression levels of THBS4 were different in different subtypes of breast cancer, and the protein expression levels of THBS1, THBS2, and THBS4 in breast cancer tissues were higher than in normal breast tissues. Survival analysis showed that breast cancer patients with high THBS1 gene expression showed worse overall survival (OS), relapse-free survival (RFS), and post-progression survival (PPS), and breast cancer patients with high THBS2 gene expression also showed worse RFS. Conversely, lower THBS3 levels predicted worse RFS, and lower THBS4 levels predicted worse OS, RFS, and distant metastasis-free survival (DMFS). Conclusions: These results suggest that THBSs may be potential biomarkers for breast cancer.

scholarly journals MicroRNA Expression in Different Sybtypes of Breast Cancer

2013 ◽  
Vol 13 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Dagnija Kalniete ◽  
Miki Nakazawa-Miklasevica ◽  
Ilze Strumfa ◽  
Arnis Abolins ◽  
Arvids Irmejs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Expression Level ◽  
Breast Cancer Patients ◽  
Event Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Tumor Tissues ◽  
Cancer Tissues

Summary Introduction. MicroRNAs are a class of small, non-coding RNA molecules able to regulate gene expression at the post-transcriptional level through binding to the 3’-UTR of the targeted mRNA, thus suppressing translation of the mRNA. In various diseases, including malignancies, expression of microRNAs is altered. Moreover, the altered expression of the microRNAs correlates with clinical and pathophysiological features of cancer thus making them good candidates for prognostic/predictive markers. Aim of the study. The aim of this study was to determine expression level of five different microRNAs (miR-10b, miR-21, miR-29a, miR-31, and miR-214) in breast cancer tissues and to look for the differences in microRNA expression between distinct subtypes of breast cancer. Material and methods. Forty five breast cancer and corresponding resection line tissues (control tissues) were studied. Breast cancer tissues were classified into the subtypes of triple-negative (23), luminal-A (13), luminal-B (7), and HER2+ (2). Quantitative analysis of miR-10b, miR-21, miR-29a, miR-31, and miR-214 was performed by real-time PCR. The expression levels of microRNAs were normalized by the expression of the reference gene RNU6B. The event-free survival in regard of high and low expression levels of microRNAs were analyzed by Log-rank (Mantel Cox) and Gehan-Breslow-Wilcoxon tests. Results. Expression levels of four microRNAs (miR-21, miR-29a, miR-31, and miR-214) were significantly higher in cancer tissues than in corresponding resection line tissues. Breast cancer patients with low expression level of miR-21 showed a trend of better event-free survival than breast cancer patients with high expression level of miR-21; however, this trend did not reach statistical significance. In triple-negative tumor tissues, miR-21, miR-29a, and miR-31 showed significantly higher expression level than in luminal-A tumor tissues. Expression levels of miR-21 and miR-29a were significantly higher in triple-negative tumor tissues than in luminal-B tumor tissues. Conclusions. Breast cancer patients with high expression level of miR-21 in tumor tissues show a trend of worse event-free survival, though; this trend did not reach statistical significance. Different microRNA expression in distinct subtypes of breast cancer points to the genetic heterogeneity of breast cancer, different regulatory targets and signaling pathways

scholarly journals Solid Plasmonic Substrates for Breast Cancer Detection by Means of SERS Analysis of Blood Plasma

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1212 ◽  
Author(s):  
Gabriela Fabiola Știufiuc ◽  
Valentin Toma ◽  
Mihail Buse ◽  
Radu Mărginean ◽  
Gabriela Morar-Bolba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Plasma ◽  
Cancer Patients ◽  
Cancer Detection ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Filtration Method ◽  
Healthy Donors ◽  
Surface Enhanced ◽  
Surface Enhanced Raman

Surface enhanced Raman spectroscopy (SERS) represents a promising technique in providing specific molecular information that could have a major impact in biomedical applications, such as early cancer detection. SERS requires the presence of a suitable plasmonic substrate that can generate enhanced and reproducible diagnostic relevant spectra. In this paper, we propose a new approach for the synthesis of such a substrate, by using concentrated silver nanoparticles purified using the Tangential Flow Filtration method. The capacity of our substrates to generate reproducible and enhanced Raman signals, in a manner that can allow cancer detection by means of Multivariate Analysis (MVA) of Surface Enhanced Raman (SER) spectra, has been tested on blood plasma samples collected from 35 healthy donors and 29 breast cancer patients. All the spectra were analyzed by a combined Principal Component-Linear Discriminant Analysis. Our results facilitated the discrimination between healthy donors and breast cancer patients with 90% sensitivity, 89% specificity and 89% accuracy. This is a direct consequence of substrates’ ability to generate diagnostic relevant spectral information by performing SERS measurements on pristine blood plasma samples. Our results suggest that this type of solid substrate could be employed for the detection of other types of cancer or other diseases by means of MVA-SERS procedure.

Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins

2021 ◽  
pp. 153537022110104
Author(s):  
Mingfei Xu ◽  
Chaoyue Liu ◽  
Lulan Pu ◽  
Jinrong Lai ◽  
Jingjia Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Tissues ◽  
Breast Tissues ◽  
Kaplan Meier Plotter

Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan–Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan–Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.

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.

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.

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