scholarly journals Differential Expression of Serum Exosomal miRNAs in Breast Cancer Patients and Healthy Controls

Author(s):  
Rahim Asgari ◽  
Jafar Rezaie

Purpose: Breast cancer has become as a serious public health concern worldwide. Breast cancer cells release exosomes into the circulatory system, which are easily accessible for further analysis like cancer diagnosis. In this study, we aimed to investigate expression of circulating exosomal miRNAs (miRs) in the serum of individuals with breast cancer and healthy controls. Methods: Exosomes were collected from serum samples using a commercial kit and characterized by scanning electron microscopy (SEM) and flow cytometry analysis. Expression of miRs such as miR-21, miR-155, miR-182, miR-373, and miR-126 were evaluated by real-time PCR. Results: The result showed that the expression level of exosomal miR-21, miR-155, miR-182, and miR-373 in the serum of breast cancer patients was higher than of those controls (P<0.05). However, expression of miR-126 did not change between breast cancer and control individuals (P>0.05). Conclusion: Our results showed a different miRs expression pattern between breast cancer and healthy samples, supposing potential biomarkers for breast cancer. Further studies focusing on these miRs are required to confirm our findings.

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini

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.


Author(s):  
Amal Ramadan ◽  
Maha Hashim ◽  
Amr Abouzid ◽  
Menha Swellam

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.


Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.


Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Tekeda F Ferguson ◽  
Sunayana Kumar ◽  
Denise Danos

Purpose: In conjunction with women being diagnosed earlier with breast cancer and a rapidly aging population, advances in cancer therapies have swiftly propelled cardiotoxicity as a major health concern for breast cancer patients. Frequent cardiotoxicity outcomes include: reduced left ventricular ejection fraction (LVEF), myocardial infarction, asymptomatic or hospitalized heart failure, arrhythmias, hypertension, and thromboembolism. The purpose of this study was to use an electronic health records system determine if an increased odds of heart disease was present among women with breast cancer. Methods: Data from the Research Action for Health Network (REACHnet) was used for the analysis. REACHnet is a clinical data research network that uses the common data model to extract electronic health records (EHR) from health networks in Louisiana (n=100,000).Women over the age of 30 with data (n=35,455) were included in the analysis. ICD-9 diagnosis codes were used to classify heart disease (HD) (Hypertensive HD, Ischemic HD, Pulmonary HD, and Other HD) and identify breast cancer patients. Additional EHR variables considered were smoking status, and patient vitals. Chi-square tests, crude, and adjusted logistic regression models were computed utilizing SAS 9.4. Results: Utilizing diagnoses codes our study team has estimated 28.6% of women over the age of 30 with a breast cancer diagnosis (n=816) also had a heart disease diagnosis, contrasted with 15.6% of women without a breast cancer diagnosis. Among patients with heart disease, there was no significant difference in the distribution of the type of heart disease diagnoses by breast cancer status (p=0.87). There was a 2.21 (1.89, 2.58) crude odds ratio of having a CVD diagnoses among breast cancer cases when referenced to cancer free women. After adjusting for age (30-49, 50-64, 65+), race (black/white), and comorbidities (obesity/overweight, diabetes, current smoker) there was an increased risk of heart disease (OR: 1.24 (1.05, 1.47)). Conclusion: The short-term and long-term consequences of cardiotoxicity on cancer treatment risk-to-benefit ratio, survivorship issues, and competing causes of mortality are increasingly being acknowledged. Our next efforts will include making advances in predictive risk modeling. Maximizing benefits while reducing cardiac risks needs to become a priority in oncologic management and monitoring for late-term toxic effects.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chumei Huang ◽  
Zhuangjian Ye ◽  
Jianxin Wan ◽  
Jianbo Liang ◽  
Min Liu ◽  
...  

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.


2020 ◽  
Vol 21 (19) ◽  
pp. 7427
Author(s):  
Iris Garrido-Cano ◽  
Vera Constâncio ◽  
Anna Adam-Artigues ◽  
Ana Lameirinhas ◽  
Soraya Simón ◽  
...  

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.


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