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 ◽  
...  

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.



2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  

Abstract Background: Breast cancer is one of the most common cancers among females with high morbidity and mortality. MicroRNAs (miRNAs) have been reported to play important roles in the development of cancers. However, the prognostic value of microRNA-421 (miR-421) in breast cancer have not been extensively explored.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the relative expression of miR-421 in breast cancer tissue samples. Relationships between miR-421 expression and clinicopathological factors were analyzed by chi-square test. The effects of several variables on survival status were tested by Kaplan-Meier curve and Cox proportional hazards regression analyses.Results: MiR-421 expression was significantly decreased in breast cancer tissues, compared with adjacent noncancerous tissues (P<0.001). Moreover, abnormal miR-421 expression was closely correlated with lymph node metastasis (P<0.001), TNM stage (P=0.021), and differentiation (P=0.044) of breast cancer patients. Kaplan-Meier analysis revealed that patients with low miR-421 expression had a shorter overall survival time than those with high miR-421 expression (P=0.001). Furthermore, multivariate analysis demonstrated that miR-421 (P=0.014, HR=2.000, 95%CI: 1.149-3.480) was an independent prognostic indicator in breast cancer patients, as well as lymph node metastasis (P=0.016, HR=1.987, 95%CI: 1.137-3.474).Conclusion: The reduced expression of miR-421 may predict the poor prognosis of breast cancer and miR-421 may be involved in the progression of breast cancer.



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.



2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang

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.



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.



2016 ◽  
Vol 25 (4) ◽  
pp. 763-768
Author(s):  
Aseem Kumar Anshu ◽  
Akhileshwari Nath ◽  
Prinyanka ◽  
Neha Sinha ◽  
Priyanka Sinha ◽  
...  


PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0118647 ◽  
Author(s):  
Yanyan Wang ◽  
Yujie Zhang ◽  
Chi Pan ◽  
Feixia Ma ◽  
Suzhan Zhang


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.



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