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 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 Nuclear ING3 Expression Is Correlated With a Good Prognosis of Breast Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaoyan Wu ◽  
Chuang Chen ◽  
Bin Luo ◽  
Dandan Yan ◽  
Honglin Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Histological Grade ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Positive Type ◽  
Cox Regression Analysis ◽  
Cancer Tissues ◽  
Breast Tissues

The inhibitor of growth (ING) family was discovered as the type II tumor suppressors, which regulated the proliferation, apoptosis, differentiation, angiogenesis, metastasis, and invasion of tumor cells through multiple pathways. ING3, a new member of ING family, has been reported to be downregulated in several types of tumors. However, few studies on ING3 in breast cancer have been reported. In this study, we investigated the expression of ING3 and determined its prognostic value in breast cancer. The immunohistochemistry was performed to evaluate the expression of ING3 in tissue microarrays (TMA) including breast cancer tissues (n=211) and normal breast tissues (n=50). In normal breast tissues, ING3 protein was detected in both the cytoplasm and nucleus. In breast cancer tissues, ING3 protein was principally detected in the cytoplasm. Compared with normal breast tissues, the expression of ING3 in nucleus was remarkably reduced in breast cancer tissues. The downregulated ING3 in nucleus was significantly correlated with clinicopathological characteristics including histological grade, lymph node metastasis, and the status of ER and PR. In HER2 positive-type and triple-negative breast cancer (TNBC) patients, it had the lower rate of nuclear ING3 with high expression than that in luminal-type. Moreover, Kaplan-Meier curves demonstrated that the reduced expression of ING3 in nucleus was correlated with a poorer 5-DFS and 5-OS of breast cancer patients. Importantly, multivariate Cox regression analysis suggested that the reduced expression of ING3 in nucleus was an independent prognostic factor in breast cancer. Our study comprehensively described the expression of ING3 in breast cancer for the first time and proved that it was an independent prognostic predictor of breast cancer, as well as a new idea for study of breast cancer.

scholarly journals Meta-analysis of the clinicopathological significance of miRNA-145 in breast cancer

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Peng Lv ◽  
Zhenzhu Zhang ◽  
Li Hou ◽  
Yayue Zhang ◽  
Lingeng Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Patients ◽  
Human Cancer ◽  
Meta Analysis ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Low Expression

Abstract Low expression of tumor suppressor microRNA (miRNA) and high expression of carcinogenic miRNA promote the occurrence and progression of human cancer. Most studies show that miR-145 is a tumor suppressor miRNA, and is closely related to the clinicopathology of breast cancer. However, the results are still inconsistent. Therefore, we conducted a meta-analysis on the basis of eligible studies to summarize the possible correlation between miR-145 and the clinicopathology and prognosis of breast cancer. Using PubMed, Embase, Web of Science, Wanfang and CNKI, we searched all published papers written in either English or Chinese on miR-145 expression in breast cancer from 1990 to November 2019 for meta-analysis. We used standardized mean difference (SMD) to evaluate the differential expression of miR-145 in breast cancer tissues and adjacent normal tissues or normal breast tissues. We found that miR-145 expression was significantly lower in breast cancer tissues than that in adjacent normal tissues (SMD = −2.93, P<0.0001) and in healthy women (SMD = −0.52, P=0.009). miR-145 expression was lower in breast cancer patients with ER-positive (SMD = 0.65, P<0.001), HER-2-positive (SMD = −1.04, P<0.001), compared with their counterparts, respectively. In addition, breast cancer patients with low expression of miR-145 had larger tumor diameters (SMD = −1.97, P<0.001) and lymph node metastasis (SMD = −1.75, P<0.001) that are unfavorable prognostic factors. Conclusion: Low miR-145 is observed in breast cancer, which is closely related to molecular subtypes and unfavorable factors of breast cancer. These findings indicate that miR-145 is tumor suppressor miRNA, and may be a potential diagnostic and prognostic marker in breast cancer.

scholarly journals Reduced Expression of GPX3 in Breast Cancer Patients in Correlation with Clinical Significance

2020 ◽  
Vol 07 (03) ◽  
pp. 087-091
Author(s):  
Pensri Saelee ◽  
Tanett Pongtheerat ◽  
Thanet Sophonnithiprasert
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Normal Breast ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chain Reaction ◽  
Messenger Ribonucleic Acid ◽  
Polymerase Chain ◽  
Breast Tissues

AbstractGlutathione peroxidase 3 (GPX3) is the main antioxidant enzyme in plasma. Its biological roles are to protect cells from oxidative stress-induced damage. Several studies have been reported the association between GPX3 expression and its correlation with cancer carcinogenesis including breast cancer. The aim of this research was to investigate the GPX3 messenger ribonucleic acid (mRNA) expression in 82 breast tumors and paired normal breast tissues by SYBR green quantitative real-time reverse transcription-polymerase chain reaction and the association with clinicopathological data. Our results show that GPX3 reduced expression was found significantly associated with number of metastatic lymph nodes (odds ratio [OR] = 3.41, 95% confidence interval [CI] = 1.35–8.64, p = 0.01), no distant metastasis (OR = 5.52, 95% CI = 3.74–11.89, p = 0.04), and nonhormone usage breast cancer patients (OR = 0.19, 95% CI = 0.04–0.93, p = 0.04). This finding suggested that GPX3 plays a role in breast carcinogenesis, and might serve as a prognostic biomarker in breast cancer patients.

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.

scholarly journals Clinical impact of PTEN methylation status as a prognostic marker for breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Amal Ramadan ◽  
Maha Hashim ◽  
Amr Abouzid ◽  
Menha Swellam
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Prognostic Marker ◽  
Methylation Status ◽  
Clinical Impact ◽  
Breast Cancer Patients ◽  
Duct Carcinoma ◽  
Cancer Group ◽  
And Control

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.

Repression of protocadherin 17 is correlated with elevated angiogenesis and hypoxia markers in female patients with breast cancer

2021 ◽  
pp. 1-10
Author(s):  
Sanaa A. El-Benhawy ◽  
Samia A. Ebeid ◽  
Nadia A. Abd El Moneim ◽  
Rabie R. Abdel Wahed ◽  
Amal R.R. Arab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Stage ◽  
Suppressor Gene ◽  
Normal Breast ◽  
Vital Role ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Cd34 Cells ◽  
Breast Tissues

BACKGROUND: Altered cadherin expression plays a vital role in tumorigenesis, angiogenesis and tumor progression. However, the function of protocadherin 17 (PCDH17) in breast cancer remains unclear. OBJECTIVE: Our target is to explore PCDH17 gene expression in breast carcinoma tissues and its relation to serum angiopoietin-2 (Ang-2), carbonic anhydrase IX (CAIX) and % of circulating CD34+ cells in breast cancer patients (BCPs). METHODS: This study included Fifty female BCPs and 50 healthy females as control group. Cancerous and neighboring normal breast tissues were collected from BCPs as well as blood samples at diagnosis PCDH17 gene expression was evaluated by RT-PCR. Serum Ang-2, CAIX levels were measured by ELISA and % CD34+ cells were assessed by flow cytometry. RESULTS: PCDH17 was downregulated in cancerous breast tissues and its repression was significantly correlated with advanced stage and larger tumor size. Low PCDH17 was significantly correlated with serum Ang-2, % CD34+ cells and serum CAIX levels. Serum CAIX, Ang-2 and % CD34+ cells levels were highly elevated in BCPs and significantly correlated with clinical stage. CONCLUSIONS: PCDH17 downregulation correlated significantly with increased angiogenic and hypoxia biomarkers. These results explore the role of PCDH17 as a tumor suppressor gene inhibiting tumor growth and proliferation.

scholarly journals Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis

Oncotarget ◽  
2016 ◽  
Vol 7 (9) ◽  
pp. 10373-10385 ◽  
Author(s):  
Weige Tan ◽  
Qian Li ◽  
Kai Chen ◽  
Fengxi Su ◽  
Erwei Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Estrogen Receptor Beta ◽  
Breast Cancer Patients ◽  
Receptor Beta

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.

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