scholarly journals Identification of Hsa_circ_0104824 as a Potential Biomarkers for Breast Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382096074
Author(s):  
Xiaohan Li ◽  
Fang Ma ◽  
Ligang Wu ◽  
Xu Zhang ◽  
Jinhai Tian ◽  
...  

Background: To study the specific expression of circular RNA (circRNA) in breast cancer and adjacent normal tissues to identify differentially expressed circRNA in breast cancer patients. To study the correlation between circRNA and clinical data of breast cancer, and to evaluate its potential as a breast cancer biomarker. Methods: The differential expression of circRNAs between the breast cancer tissues and adjacent normal tissues was screened by Human CircRNA Microarray. Candidate circRNAs verified by qRT-PCR. CircRNA was analyzed by Agilent GeneSpring 13.0 software. SPSS23.0, GraphPad Prism, and Sigmaplot software were used for statistical analysis. Perform T test, one-way ANOVA, curve regression analysis and ROC curve analysis for evaluating the diagnostic value of circular RNA. Results: Among the 2021 differentially expressed circRNAs, 546 were up-regulated and 1475 were down-regulated in breast cancer tissues. The validation study demonstrated that six circRNAs were downregulated. Among them, hsa_circ_0104824 proved high correlation between breast cancer tissues and plasma samples in its expression and diagnostic value. Conclusion: Hsa_circ_0104824 may serve as a promising predictive biomarker and therapeutic target for patients with breast cancer.

2021 ◽  
Vol 11 ◽  
Author(s):  
Min Wu ◽  
Pan Zhang ◽  
Penghui Wang ◽  
Zhen Fang ◽  
Yaqin Zhu

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Lin Cheng ◽  
Yu-Zhou Huang ◽  
Wei-Xian Chen ◽  
Liang Shi ◽  
Zhi Li ◽  
...  

Abstract Cell division cycle protein (CDC20) has been observed to be expressed higher in various kinds of human cancers and was associated with poor prognosis. However, studies on role of CDC20 in breast cancer are seldom reported till now, most of which are not systematic and conclusive. The present study was performed to analyze the expression pattern, potential function, and distinct prognostic effect of CDC20 in breast cancer using several online databases including Oncomine, bc-GenExMiner, PrognoScan, and UCSC Xena. To verify the results from databases, we compared the mRNA CDC20 expression in breast cancer tissues and adjacent normal tissues of patients by real-time PCR. We found that CDC20 was expressed higher in different types of breast cancer, comparing with normal tissues. Moreover, the patients with a more advanced stage of breast cancer tended to express higher level CDC20. CDC20 was expressed higher in breast cancer tissues than normal tissues from patients in our hospital, consistent with the results from databases. Estrogen receptor (ER) and progesterone receptor (PR) status were negatively correlated with CDC20 level. Conversely, Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to CDC20 expression in breast cancer patients with respect to normal individuals. Higher CDC20 expression correlated with worse survival. Finally, a positive correlation between CDC20 and Targeting protein for Xenopus kinesin-like protein 2 (TPX2) expression was revealed. CDC20 could be considered as a potential predictive indicator for prognosis of breast cancer with co-expressed TPX2 gene.


2021 ◽  
Author(s):  
shaohua chen ◽  
Ziyao Jin ◽  
Linfeng Xin ◽  
Lv Lv ◽  
Xuemei Zhang ◽  
...  

Abstract BackgroundThe aim of this study is to investigate the potential clinical and prognostic value, role and driving molecular mechanisms of the origin recognition complex family in breast cancer.Resultsata from Oncomine, TCGA, GEO and ULCAN showed that ORC1L and ORC6L were highly expressed in breast cancer tissues, while the expression of ORC5L was inconsistent and there was no significant difference in the expression of ORC2L, ORC3L and ORC4L. High expression of ORC1L and ORC6L were mainly Her2 overexpressed subtype, and their expression were negatively correlated with patient age and positively correlated with tumor size, but not with lymph node metastasis, distant metastasis, or tumor stage. Expression of ORC5L was also negatively correlated with age and positively correlated with lymph node metastasis, but not with breast cancer molecular subtype and tumor size. Expression of ORC1L and ORC5L had high diagnostic value, and ORC6L had the highest diagnostic value in breast cancer. ORC6L was an independent poor prognostic factor for overall survival of breast cancer patients. It was involved in cell cycle progression, cell senescence, epigenetic regulation and other biological functions, and may regulate signaling pathways such as NF-KB, TP53 and WNT in breast cancer. We also found that the expression of ORC6L was related to the increased infiltration of Th1/2 cell and Treg cell, and decreased infiltration of Mast cell and NK cell.ConclusionsORC1L and ORC6L are highly expressed in breast cancer tissues, of which ORC6L has high diagnostic value and is an independent poor prognostic factor for overall survival of breast cancer patients. ORC6L may be involved in the occurrence and progression of breast cancer by regulating cell cycle progression, promoting the activation of cancer signaling pathways, and influencing tumor immune cells infiltration.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yongxia Zhang ◽  
Fengjie Liu ◽  
Han Zhang ◽  
Heng Ma ◽  
Jian Sun ◽  
...  

PurposeTo evaluate the value of radiomics analysis in contrast-enhanced spectral mammography (CESM) for the identification of triple-negative breast cancer (TNBC).MethodCESM images of 367 pathologically confirmed breast cancer patients (training set: 218, testing set: 149) were retrospectively analyzed. Cranial caudal (CC), mediolateral oblique (MLO), and combined models were built on the basis of the features extracted from subtracted images on CC, MLO, and the combination of CC and MLO, respectively, in the tumour region. The performance of the models was evaluated through receiver operating characteristic (ROC) curve analysis, the Hosmer-Lemeshow test, and decision curve analysis (DCA). The areas under ROC curves (AUCs) were compared through the DeLong test.ResultsThe combined CC and MLO model had the best AUC and sensitivity of 0.90 (95% confidence interval: 0.85–0.96) and 0.97, respectively. The Hosmer–Lemeshow test yielded a non-significant statistic with p-value of 0.59. The clinical usefulness of the combined CC and MLO model was confirmed if the threshold was between 0.02 and 0.81 in the DCA.ConclusionsMachine learning models based on subtracted images in CESM images were valuable for distinguishing TNBC and NTNBC. The model with the combined CC and MLO features had the best performance compared with models that used CC or MLO features alone.


2019 ◽  
Author(s):  
Libin WANG ◽  
Xiaohan LI ◽  
Danni WANG ◽  
Huimin FENG ◽  
Fang MA ◽  
...  

Abstract Background : To investigate the characteristic expression of circular RNAs between breast cancer and para-carcinoma tissue, identified hsa-circ-000696 as a novel biomarker for breast cancer. Methods: 136 patients were recruited in General Hospital of NingXia Medical Universit. Of which 3 patients tissue for microarray analysis, 20 and 113 patients for circRNA expression in tissue and peripheral blood, respectively. The candidate circRNAs was verified by qPCR in BC patients’ tissue and peripheral blood. GeneSpring 13.0(Agilent) software were used for analysis the circRNA array data. CircRNA structure were performed by circPrimer1.2 software. MiRanda v3.3,RNAhybrid 2.1 and Cytoscape 3.6.0 were utilized as tools to predict the circRNA-miRNA networks. T-test, Curve regression analysis and ROC analysis were performed to determine the diagnostic values of candidate circRNAs. Statistical analysis was performed using SPSS23.0 software. Results: 2021 differentially expressed circRNAs were identified, of which 546 were upregulated and 1475 were downregulated. Four circRNAs were selected with filter criteria for further verify in BC tissues. Hsa-circ-0006969 was significantly downregulated both in breast cancer tissues and peripheral blood. Hsa-circ-0006969 proved a highest diagnostic value in breast cancer tissues(AUC=0.889), peripheral blood(AUC=0.823) for Grade 1(AUC=0.672), Grade 3(AUC=0.675), ER positive(AUC=0.648), TNM Ⅰ(AUC=0.687) and TNM Ⅱ(AUC=0.769), TNM Ⅲ(AUC=0.757), TNM early stage(Ⅰ, Ⅱ) (AUC=0.751). Hsa-circ-0006969 show more effective diagnostic values of for tumor metastasis (AUC=0.742) compared with CA153 (AUC=0.712). Conclusion: Has-circ-0006969 could be a novel predictive biomarker for diagnostic and treatment of breast cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qian Zhou ◽  
Xiaofeng Liu ◽  
Mingming Lv ◽  
Erhu Sun ◽  
Xun Lu ◽  
...  

Background. Breast cancer is one of the most commonly diagnosed cancers all over the world, and it is now the leading cause of cancer death among females. The aim of this study was to find DEGs (differentially expressed genes) which can predict poor prognosis in breast cancer and be effective targets for breast cancer patients via bioinformatical analysis. Methods. GSE86374, GSE5364, and GSE70947 were chosen from the GEO database. DEGs between breast cancer tissues and normal breast tissues were picked out by GEO2R and Venn diagram software. Then, DAVID (Database for Annotation, Visualization, and Integrated Discovery) was used to analyze these DEGs in gene ontology (GO) including molecular function (MF), cellular component (CC), and biological process (BP) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway. Next, STRING (Search Tool for the Retrieval of Interacting Genes) was used to investigate potential protein-protein interaction (PPI) relationships among DEGs and these DEGs were analyzed by Molecular Complex Detection (MCODE) in Cytoscape. After that, UALCAN, GEPIA (gene expression profiling interactive analysis), and KM (Kaplan–Meier plotter) were used for the prognostic information and core genes were qualified. Results. There were 96 upregulated genes and 98 downregulated genes in this study. 55 upregulated genes were selected as hub genes in the PPI network. For validation in UALCAN, GEPIA, and KM, 5 core genes (KIF4A, RACGAP1, CKS2, SHCBP1, and HMMR) were found to highly expressed in breast cancer tissues with poor prognosis. They differentially expressed between different subclasses of breast cancer. Conclusion. These five genes (KIF4A, RACGAP1, CKS2, SHCBP1, and HMMR) could be potential targets for therapy in breast cancer and prediction of prognosis on the basis of bioinformatical analysis.


2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Peng Lv ◽  
Zhenzhu Zhang ◽  
Li Hou ◽  
Yayue Zhang ◽  
Lingeng Lu ◽  
...  

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&lt;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&lt;0.001), HER-2-positive (SMD = −1.04, P&lt;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&lt;0.001) and lymph node metastasis (SMD = −1.75, P&lt;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.


2021 ◽  
Author(s):  
Yao Xu ◽  
Ya-Wen Wang ◽  
Xu Chen ◽  
Can Liu ◽  
Yan-Duo Chen ◽  
...  

Abstract Background Emerging evidence shows that circular RNAs (circRNAs) play crucial parts in tumorigenesis and progression. In this work, the expression, clinical significance, function and potential mechanism of circ_0075796 in breast cancer were explored. Methods The expression of circ_0075796 in 189 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were conducted for cell proliferation. Transwell assay and wound healing assay were used for cell migration and invasion. Flow cytometry analysis was adopted for cell cycle and cell apoptosis. The cellular localization of circ_0075796 was determined by fluorescence in situ hybridization (FISH). The circ_0075796/miR-452-3p/SAMD5 axis was screened out by bioinformatics analysis and verified by qRT-PCR. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m6A) modification levels of circ_0075796. QRT-PCR was used to detect the expression of RNA binding protein Quaking (QKI) in breast cancer tissues and adjacent normal tissues. Results circ_0075796 was downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, circ_0075796 showed satisfactory diagnostic value to discriminate breast cancer and normal controls. Downregulated circ_0075796 expression was correlated with lymph node metastasis, HER2 expression, larger tumor size, high Ki-67 expression, advanced histological grade, aggressive molecular subtypes and advanced clinical stages. Overexpression of circ_0075796 inhibited cell proliferation, migration and invasion in vitro. FISH showed that circ_0075796 was localized in the cytoplasm and nucleus of breast cancer cells. Bioinformatics analysis and qRT-PCR revealed the potential circ_0075796/miR-452-3p/SAMD5 axis. Moreover, circ_0075796 showed lower m6A modification levels in breast cancer tissues compared to adjacent normal tissues. QKI was predicted to contain binding sites of circ_0075796 and was downregulated in breast cancer tissues compared to adjacent normal controls. Conclusions circ_0075796 was downregulated in breast cancer compared to normal controls, and showed potential diagnostic value for breast cancer. Downregulation of circ_0075796 was correlated with aggressive clinical features of breast cancer and overexpression of circ_0075796 inhibited the progression of breast cancer in vitro, indicating that circ_0075796 may be related to tumorigenesis and development of breast cancer.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined public microarray data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified the Fc receptor like B, encoded by FCRLB, as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of FCRLB messenger RNA than did patients not treated with trastuzumab, demonstrating increased primary tumor expression of a receptor for an immunoglobulin Fc domain with specific expression in B-lymphocytes (5) as a transcriptional consequence of treatment with trastuzumab.


Sign in / Sign up

Export Citation Format

Share Document