MicroRNA profiling in serum: Potential signatures for breast cancer diagnosis

2020 ◽  
pp. 1-13
Author(s):  
Xuan Zou ◽  
Tiansong Xia ◽  
Minghui Li ◽  
Tongshan Wang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Expression Patterns ◽  
External Validation ◽  
Breast Cancer Diagnosis ◽  
Serum Samples ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Serum Exosomes

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC.

scholarly journals Non-Invasive Biomarkers for Early Detection of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2767
Author(s):  
Jiawei Li ◽  
Xin Guan ◽  
Zhimin Fan ◽  
Lai-Ming Ching ◽  
Yan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
False Negative ◽  
Breast Cancer Diagnosis ◽  
Diagnostic Biomarkers ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Common Cancer ◽  
Volatile Organic

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

scholarly journals Clinical Significance of Annexin A2 Expression 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 ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

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.

scholarly journals Exosomes: A Forthcoming Era of Breast Cancer Therapeutics

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4672
Author(s):  
Banashree Bondhopadhyay ◽  
Sandeep Sisodiya ◽  
Faisal Abdulrahman Alzahrani ◽  
Muhammed A. Bakhrebah ◽  
Atul Chikara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Breast Cancer Patients ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Circulating Markers

Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

Identification of non-invasive biomarkers for early detection of breast cancer: A Review

2021 ◽  
Vol 2 (1) ◽  
pp. 01-05
Author(s):  
Asima Tayyab
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Potential Role ◽  
Small Volume ◽  
Breast Cancer Diagnosis ◽  
Diagnostic Purpose ◽  
Diagnose Breast Cancer ◽  
Non Invasive ◽  
Early Stages

Despite decades of research, diagnostic tests with specificity and accuracy for early breast cancer are yet unavailable. Major problems associated with poor diagnosis are either due to incompetency of reported biomarkers or small volume of patients under study. Moreover, heterogeneity of the disease further complicates the struggle of identifying effective biomarkers. Therefore, to improve the survival rate, look for new, sensitive and specific biomarkers for early breast cancer diagnosis is need of hour. In this study, we have reviewed recently reported serum biomarkers and categorized them based on their biomolecular nature such as protein, ctDNA, epigenetics regulation and miRNA. Potential role of these available biomarkers in early diagnosis of breast cancer has also been discussed. Based on the facts obtained from literature review, it is revealed that using any individual biomolecule as a biomarker is not sufficient to diagnose breast cancer at early stages rather it is suggested that a panel of proteins or miRNAs would offer better sensitivity and specificity. Whereas, unavailability of a potential ctDNA and epigenetics regulation candidate for diagnostic purpose is and suggest the use of more sophisticated techniques to unwound these regulations in serum especially at early stages of breast cancer.

Certain Study on Improvement of Bandwidth in 3GHz Microstrip Patch Antenna Designs and Implemented on Monostatic Radar Approach for Breast Cancer Diagnosis in Microwave Imaging System

2015 ◽  
Vol 25 (02) ◽  
pp. 1650006 ◽  
Author(s):  
K. Sakthisudhan ◽  
N. Saravana Kumar
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Imaging System ◽  
Breast Cancer Diagnosis ◽  
Patch Antennas ◽  
Human Breast ◽  
Test Bed ◽  
Microstrip Patch Antennas ◽  
Microstrip Patch ◽  
Tumor Tissues

A 3[Formula: see text]GHz class of an EF and [Formula: see text] shaped Microstrip Patch Antennas (MPAs) designed, simulated and fabricated has been presented in this paper. These simulated designs with appropriate parameters are implemented on the fabrication prototypes which have been validated with help of Agilent Microwave Analyzer (N99917A). These proposed MPAs and dielectric equivalent human breast model that have been validated using the different dielectric strengths of coupling mediums are presented. These MPAs and dielectric equivalent human breast model have been validated using the existing Debye test bed. The coverage and vector dimension of tumor tissues have been detected using the Monostatic radar approach in the EF and [Formula: see text] shaped MPAs-based existing Debye test bed setups. This paper conclude that Fractional Bandwidth (FBW) of EF shaped MPA is 26.79% greater than [Formula: see text] shaped MPA of 21.67%. Hence, the EF and [Formula: see text] shaped MPAs prototypes are suitable for breast cancer diagnosis systems. The prototypes’ depth, coverage and vector dimensions are presented in this paper.

scholarly journals Deep Learning-Based Breast Cancer Diagnosis at Ultrasound: Initial Application of Weakly-Supervised Algorithm Without Image Annotation Original Research

2021 ◽  
Author(s):  
Jaeil Kim ◽  
Hye Jung Kim ◽  
Chanho Kim ◽  
Jin Hwa Lee ◽  
Keum Won Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Image Annotation ◽  
Characteristic Curve ◽  
External Validation ◽  
Region Of Interest ◽  
Breast Cancer Diagnosis ◽  
Original Research ◽  
Internal Validation ◽  
Weakly Supervised

Abstract Conventional deep learning (DL) algorithm requires full supervision of annotating the region of interest (ROI) that is laborious and often biased. We aimed to develop a weakly-supervised DL algorithm that diagnosis breast cancer at ultrasound without image annotation. Weakly-supervised DL algorithms were implemented with three networks (VGG16, ResNet34, and GoogLeNet) and trained using 1000 unannotated US images (500 benign and 500 malignant masses). Two sets of 200 images (100 benign and 100 malignant masses) were used for internal and external validation sets. For comparison with fully-supervised algorithms, ROI annotation was performed manually and automatically. Diagnostic performances were calculated as the area under the receiver operating characteristic curve (AUC). Using the class activation map, we determined how accurately the weakly-supervised DL algorithms localized the breast masses. For internal validation sets, the weakly-supervised DL algorithms achieved excellent diagnostic performances, with AUC values of 0.92–0.96, which were not statistically different (all Ps > 0.05) from those of fully-supervised DL algorithms with either manual or automated ROI annotation (AUC, 0.92–0.96). For external validation sets, the weakly-supervised DL algorithms achieved AUC values of 0.86–0.90, which were not statistically different (Ps > 0.05) or higher (P = 0.04, VGG16 with automated ROI annotation) from those of fully-supervised DL algorithms (AUC, 0.84–0.92). In internal and external validation sets, weakly-supervised algorithms could localize 100% of malignant masses, except for ResNet34 (98%). The weakly-supervised DL algorithms developed in the present study were feasible for US diagnosis of breast cancer with well-performing localization and differential diagnosis.

Genome-wide DNA methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

2020 ◽  
Author(s):  
Zhihong Gong ◽  
Jianhong Chen ◽  
Jie Wang ◽  
Song Liu ◽  
Christine B. Ambrosone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Racial Differences ◽  
Mirna Expression ◽  
Expression Patterns ◽  
European Ancestry ◽  
Integrated Analysis ◽  
American Women ◽  
Mirna Genes ◽  
Genome Wide

Abstract Background: Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). The reasons remain largely unknown. Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- breast cancer, and their functional role in the regulation of miRNA expression, especially among high risk AA women. Methods: In this study, genome-wide DNA methylation and miRNA expression profiling was performed using the Illumina Infinium HumanMethylation450 Bead Chip platform and miRNA sequencing (miRNA-seq) in breast tumors from both AA and EA women. Results: The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, which correspond to 2,035 unique mature miRNAs. Cluster analysis of these miRNA-associated methylation loci showed a clear pattern of ER-subtype differences. We identified differentially methylated loci (DMLs: (|delta β|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis of DNA methylation and corresponding miRNA expression identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. Further target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor, cytoskeleton remodeling, angiogenesis, EMT, and others such as signal transduction TGF-β, Wnt, NOTCH, and ESR1-mediated signaling pathways. Conclusions: Our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings shed light on the epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes and to serve as potential preventative and therapeutic targets.

Diagnostic value of oncofetal miRNAs in cancers: A comprehensive analysis of circulating miRNAs in pan-cancers and UCB

2021 ◽  
pp. 1-18
Author(s):  
Xin Zhou ◽  
Cheng Liu ◽  
Yin Yin ◽  
Cheng Zhang ◽  
Xuan Zou ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Diagnostic Value ◽  
Comprehensive Analysis ◽  
Detection Methods ◽  
Plasma Samples ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Chinese Populations ◽  
Non Invasive ◽  
Plasma Mirnas

BACKGROUND: Circulating miRNAs are promising biomarkers for detection of various cancers. As a “developmental” disorder, cancer showed great similarities with embryos. OBJECTIVE: A comprehensive analysis of circulating miRNAs in umbilical cord blood (UCB) and pan-cancers was conducted to identify circulating miRNAs with potential for cancer detection. METHODS: A total of 3831 cancer samples (2050 serum samples from 15 types of cancers and 1781 plasma samples from 13 types of cancers) and 248 UCB samples (120 serum and 128 plasma samples) with corresponding NCs from Chinese populations were analyzed via consistent experiment workflow with Exiqon panel followed by multiple-stage validation with qRT-PCR. RESULTS: Thirty-four serum and 32 plasma miRNAs were dysregulated in at least one type of cancer. Eighteen serum and 16 plasma miRNAs were related with embryos. Among them, 9 serum and 8 plasma miRNAs with consistent expression patterns between pan-cancers and UCB were identified as circulating oncofetal miRNAs. Retrospective analysis confirmed the diagnostic ability of circulating oncofetal miRNAs for specific cancers. And the oncofetal miRNAs were mainly up-regulated in tissues of pan-cancers. CONCLUSIONS: Our study might serve as bases for the potential application of the non-invasive biomarkers in the future clinical.

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