Diagnostic Value For Breast Cancer Research Articles

Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer

BackgroundBreast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated.MethodsRNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3.ResultsUsing RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients.ConclusionsOur study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

The Implication of Growth Arrest-Specific 5 rs145204276 Polymorphism and Serum Expression of Sirtuin 1, Transforming Growth Factor-Beta, and microRNA-182 in Breast Cancer.

Breast cancer (BC) patients have a higher chance of survival if it is diagnosed at an early stage, which is essential for efficient treatment of the condition. The results of an elevated risk of cancer, including BC, previously associated with the ins/del polymorphism rs145204276 in the promoter region of growth arrest-specific 5 (GAS5) are still up for debate. Thus, this study aimed to appraise the frequency of the GAS5 rs145204276 variant with BC risk and demonstrate the potential impact of the sirtuin 1 (SIRT-1), transforming growth factor-beta (TGF-β), and microRNA-182 (miR-182) expression and their diagnostic value in BC. Blood samples of 155 patients with BC and fibroadenoma and 80 healthy controls were analyzed for GAS5 rs145204276 single nucleotide polymorphism (SNP), SIRT-1, TGF-β, and miRNA-182 expression levels. Ins/ins genotype and ins allele frequencies for GAS5 rs145204276 were considerably higher in BC patients compared with controls. Patients with BC had significantly greater serum levels of TGF-β, miR-182, and SIRT-1 expression. The SIRT-1, TGF-β, and miR-182 genes provide novel, noninvasive diagnostic biomarkers for BC.

Identification of Serum miR-501-3p and miR-338-3p as Novel Diagnostic Biomarkers for Breast Cancer and Their Target Genes Associated with Immune Infiltration.

MicroRNAs influence the growth and metastasis of breast cancer (BC) by regulating their target genes. Our study aims to screen and identify miRNAs that are closely related to the development of breast cancer, and explore the role of these miRNAs and their target genes in breast cancer. Bioinformatics tools were applied to screen breast cancer-associated miRNAs and predict their potential target genes. Serum miRNAs were measured using RT-PCR. The correlation between miRNA expression and different clinicopathological features of BC patients was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. GEPIA, Kaplan-Meier Plotter, TIMER, and TISIDB databases were used to validate the expression levels and their prognostic value, as well as their target gene associated with immune infiltrating cells and immune checkpoints. Breast cancer-associated serum miR-338-3p and miR-501-3p were screened and verified for the first time. Serum miR-501-3p was elevated in BC and was closely linked to the ki-67 index and histological grade. CDKN2C, as a potential target gene of miR-501-3p, was enriched in the cGMP-PKG signaling pathway. Serum miR-338-3p was reduced in BC and was strongly linked to lymph node metastasis and histological grading. ACTR2, CDH1, COL1A1, RBBP5, RRM1, and TPM3, as potential target genes of miR-338-3p, were enriched in MAPK, PI3K-Akt, and RAS signaling pathways. These target genes were found to be linked to breast cancer prognosis, immune infiltrating cells, and immune checkpoint inhibitors. Analysis of ROC curve showed that serum miR-501-3p combined with serum miR-338-3p had a high diagnostic value in breast cancer (AUC: 0.89, 95% CI: 0.821-0.958). Serum miR-501-3p combined with serum miR-338-3p show obvious clinical significance in the diagnosis and prognosis of breast cancer, which suggests that they may act as novel diagnostic biomarkers for breast cancer.

Investigation of miR-133a, miR-637 and miR-944 genes expression and their relationship with PI3K/AKT signaling in women with breast cancer.

MicroRNAs (miRNAs) are regulatory molecules capable of positively or negatively regulating signaling pathways, and are involved in tumorigenesis as well as various aspects of cancer. The purpose of this study was to investigate the expression levels of miR-133a, miR-637, and miR-944 in serum and tumor tissues as well as their relationship with the expression level of phosphatidylinositol-3-kinase (PI3K) and protein kinase-B (AKT) genes and proteins along with their clinical significance in breast cancer. The expressions of miR-133a, miR-637, miR-944, PI3K, and AKT genes were examined in the tumor and tumor margin tissues of 40 patients with breast cancer, as well as the serum levels of miR-133a, miR-637, and miR-944 in these patients and 40 healthy groups by quantitative real-time PCR (qRT-PCR). PI3K and AKT proteins expression in tumor and tumor margin tissues were detected using immunohistochemistry (IHC). The expression levels of miR-133a and miR-637 in the tumor tissue and serum of patients were lower than those in the tumor margin tissue and serum of the healthy group, respectively. In addition, the expression level of miR-944 in the tumor tissue was lower than that in the tumor margin tissue, but its expression increased in the serum of cancer patients compared to that in the healthy group. The expression of miR-637 was correlated with tumor location and Her2 receptors, and the expression of miR-944 was correlated with tumor location and family history. PI3K and AKT mRNA and protein levels were higher in the tumor tissues than in the tumor margin tissues (p < 0.05). The results of our study revealed that miR-637 has a better diagnostic value in breast cancer than miR-133a and miR-944.

The Potential Role of CDH1 as an Oncogene Combined With Related miRNAs and Their Diagnostic Value in Breast Cancer.

BackgroundBreast cancer (BC) is the leading cause of cancer−related mortality in females and the most common malignancy with high morbidity worldwide. It is imperative to develop new biomarkers and therapeutic targets for early diagnosis and effective treatment in BC.MethodsWe revealed the oncogene function of cadherin 1 (CDH1) via bioinformatic analysis in BC. Moreover, miRNA database was utilized to predict miRNAs upstream of CDH1. Expression of CDH1-related miRNAs in BC and their values in BC stemness and prognosis were analyzed through TCGA‐BRCA datasets. In addition, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to explore the potential functions and signaling pathways of CDH1 in combination with CDH1-related miRNAs in BC progression. Finally, the differential expressions of soluble E-cadherin (sE-cad), which is formed by the secretion of CDH1-encoded E-cadherin into serum, analyzed by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression level of CDH1-related miRNAs in serum samples.ResultsThe mRNA and protein expressions of CDH1 were elevated in BC tissues compared with normal counterparts. Moreover, CDH1 overexpression was positively correlated with BC stage, metastatic, stemness characteristics, and poor prognosis among patients. In predictive analysis, miR-340, miR-185, and miR-20a target CDH1 and are highly expressed in BC. miR-20a overexpression alone was strongly associated with high stemness characteristics and poor prognosis of BC. Additionally, GO, KEGG, and hallmark effect gene set analysis demonstrated that CDH1 in combination with overexpression of miR-340, miR-185, or miR-20a participated in multiple biological processes and underly signaling pathways involving in tumorigenesis and development of BC. Finally, we provide experimental evidence that the combined determination of serum sE-cad and miR-20a in BC has highly diagnostic efficiency.ConclusionsThis study provides evidence for CDH1 as an oncogene in BC and suggests that miR-20a may regulate the stemness characteristics of BC to exert a pro-oncogenic effect by regulating CDH1. Moreover, sE-cad and miR-20a in serum can both be used as valid noninvasive markers for BC diagnosis.

Expression of lncRNAs AK058003 and APOC1P1 in breast cancer patients

In the current study, the expression levels of two important lncRNAs, i.e., AK058003 and APOC1P1, in breast tumors were compared with adjacent non-tumor tissues to evaluate their diagnostic potential in a panel of 121 patients. Total RNA was extracted, cDNA was synthesized and expression of AK058003 and APOC1P1 was assessed using qRT-PCR. A significant overexpression and positive correlation between these two lncRNAs were observed in tumor tissues compared to marginal healthy tissues. In conclusion, the examined lncRNAs were overexpressed in tumor tissues, suggesting their significant diagnostic value in breast cancer.

Diagnostic Value of Nonacid Nucleic Blood Tumor Marker Panels in Early Diagnosing Breast Cancer: A Systematic Review and Network Meta-Analysis.

This study is aimed at determining the best nonacid nucleic blood tumor marker panels in terms of sensitivity, specificity, and accuracy in order to detect breast cancer in early stages (I, II, and III) among eligible women for breast cancer screening. PubMed, Web of Science, Embase, Scopus, and Cochrane were systematically reviewed to assess nonacid nucleic blood tumor marker panels' diagnostic value in women, both healthy and patient (before any anticancer treatment), for detecting breast cancer. A network meta-analysis was carried out using a Bayesian network meta-analysis to estimate combined odd ratio (OR) and 95% CI credible interval for presenting the results. Rankograms plot was drawn to rank the diagnostic value of different panels. Of the 2358 titles initially identified, 9 studies and 8 panels were included in the network meta-analysis. Panels A (MMP-9/TIMP-1) and K (TF1+TF2+TF3) had the highest sensitivity in early stages, as panel A with OR = 11.61 and 95% CI (1.49-102.5) demonstrated a better function than mammography. Panels H (CA 15.3 + IL-18) and A (MMP-9/TIMP-1) had the highest specificity in early stages, but no significant difference with mammography. Panels A (MMP-9/TIMP-1) and H (CA 15.3 + IL-18) had the highest accuracy in early stages, as they significantly exhibited a higher function than mammography with OR = 6.87 and 95% CI (2.07-31.35) as well as OR = 3.44 and 95% CI (1.15-11.07), respectively. Panel A including MMP-9/TIMP-1 in early stages demonstrated a higher diagnostic value for breast cancer than the rest of the panels.

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer - A Comprehensive Bioinformatics Analysis.

ObjectiveWe aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC).MethodsKaplan–Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan–Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC.ResultsORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration.ConclusionORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

The Diagnostic Value of Serum Exosomal Has_circ_0000615 for Breast Cancer Patients.

BackgroundTo explore the expression level of has_circ_0000615 in peripheral blood samples and evaluate its diagnostic value for breast cancer patients.MethodsThe peripheral blood samples of 95 breast cancer patients who underwent curative surgical resection and 95 age-matched healthy volunteers in our institutions from September 2019 to November 2020 were systematically collected. The expression level of has_circ_0000615 in the plasma was amplified and detected by qRT-PCR, and its correlation to clinicopathological characteristics of breast cancer patients were analyzed.ResultsBreast cancer patients had a significantly higher expression level of has_circ_0000615 in the plasma than healthy controls (P < 0.01), and its high expression was closely associated with advanced tumor stage (P=0.010), lymph node metastasis (P = 0.001) and high grade of recurrence risk (P=0.012). The receiver operator characteristic (ROC) curves showed that the area under curve (AUC) value, sensitivity and specificity of has_circ_0000615 for the diagnosis of non-metastatic breast cancer was 0.904 (95% CI: 0.863–0.944), 76.8% and 88.4%, respectively. Serum has_circ_0000615 expression had a better diagnostic efficiency than routine tumor biomarkers such as CA153, CA125 and CEA for distinguishing breast cancer patients from healthy individuals. TEM revealed that isolated exosomes from the culture medium of breast cancer cells had a disk-like appearance with a diameter of 80–200 nm vesicles, and the expression of exosome markers CD9 and CD81 was markedly increased. More importantly, the expression of has_circ_0000615 was detected in the exosomes and its expression level was markedly upregulated in breast cancer cell lines compared with normal ductal epithelial cells. The stability assay showed that there was no difference between RNA extraction at 0 hour and 24 hours in terms of the expression of has_circ_0000615 (P =0.327). Has_circ_0000615 might as exosomes be secreted into the circulating blood of breast cancer patients, resulting in a high expression level in plasma samples.ConclusionThe detection of has_circ_0000615 might be a promising diagnostic method for breast cancer.

CircRNAs as promising biomarker in diagnosis of breast cancer: An updated meta-analysis.

BackgroundCircular RNAs (circRNAs) have been identified to be involved in onset and progression of multiple malignant tumors. The present study aimed to systematically evaluate the diagnostic values of circRNAs in breast cancer.MethodsThe PubMed, Web of Science, Embase, CNKI, and Wanfang online databases were searched for the relevant studies before December 31, 2020. Statistical analysis of the diagnostic tests was performed based on STATA 16.0, Meta‐DiSc 1.4, and RevMan 5.3 software. The threshold effect and publication bias were measured by the Spearman correlation and Deeks’ funnel plot asymmetry test, respectively.ResultsTwenty‐one studies from 13 articles were included in this meta‐analysis. The pooled sensitivity and specificity were 0.77 and 0.71, respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and overall diagnostic odds ratio (DOR) were 2.6, 0.33, and 8, respectively. Furthermore, the area under the summary receiver operator characteristic curve was 0.80. In addition, down‐regulated circRNAs achieved a diagnostic performance higher than up‐regulated circRNAs, with area under curve (AUC) values of 0.81 and 0.74, respectively. Studies based on tissue samples presented better diagnostic accuracy than those based on plasma samples, with AUC values of 0.80 and 0.67. In addition, two circRNAs, including circ_0001073 and circTADA2A‐E5/E6, showed higher diagnostic values, with AUC value of 0.990 and 0.937, respectively. According to the results of meta‐regression, the case size (p<0.05) might be the source of the heterogeneity.ConclusionCircRNAs exhibited a high diagnostic value for breast cancer and may function as potential diagnostic biomarkers for breast cancer.

Identification of Differentially Expressed Plasma lncRNAs As Potential Biomarkers for Breast Cancer

BackgroundBreast cancer is the most common malignant tumor in women and is not easy to diagnose. Increasing evidence has underscored that long non-coding RNAs (lncRNAs) play important regulatory roles in the occurrence and progression of many cancers, including breast cancer. We aimed to identify lncRNAs in plasma as potential biomarkers for breast cancer. Patients and MethodsWe analyzed the Gene Expression Omnibus (GEO) datasets GSE22820, GSE42568, and GSE65194 to identify the common differential genes between cancer tissues and adjacent tissues. Then 14 lncRNAs were identified among the common differential genes and validated by using real-time quantitative polymerase chain reaction in 92 patients with breast cancer and 100 healthy controls. Receiver operating characteristic (ROC) curves were constructed to evaluate their diagnostic value for breast cancer. ResultsIntegrated analysis of the GEO datasets identified three significantly upregulated and 11 downregulated lncRNAs in breast cancer tissues. Compared with healthy controls, MIAT was significantly upregulated in breast cancer patient plasma, and LINC00968 and LINC01140 were significantly downregulated. ROC curve analysis suggested that these three lncRNAs can discriminate breast cancer from healthy individual with high specificity and sensitivity. ConclusionThis research identified three differentially expressed lncRNAs in breast cancer patient plasma. Our data suggest that these three lncRNAs can be used as potential diagnostic biomarkers of breast cancer.

P049 - Methylation signatures with diagnostic value in breast cancer via automated machine learning

P049 - Methylation signatures with diagnostic value in breast cancer via automated machine learning

SIK2 Promotes Cisplatin Resistance Induced by Aerobic Glycolysis in Breast Cancer Cells through PI3K/AKT/mTOR Signaling Pathway.

This study aimed to investigate the effect of SIK2 on cisplatin resistance induced by aerobic glycolysis in breast cancer cells and its potential mechanism. qRt-PCR and Western blot were used to detect SIK2 mRNA and protein levels, and cisplatin (DDP) resistant cell lines of breast cancer cells were established. Viability was measured and evaluated via CCK-8, cell invasion capability was evaluated via Transwell, and apoptosis rate was assessed via Flow cytometry. The glycolysis level was evaluated by measuring glucose consumption and lactic acid production. The protein levels of p-PI3K, p- protein kinase B (Akt) and p-mTOR were determined by western blot. SIK2 was highly expressed in breast cancer tissues and cells compared with adjacent tissues and normal human breast epithelial cells, and it had higher diagnostic value for breast cancer. Silencing SIK2 expression can inhibit proliferation and invasion of breast cancer cells and induce their apoptosis. In addition, SIK2 knockdown inhibits glycolysis, reverses the resistance of drug-resistant cells to cisplatin, and inhibits PI3K/AKT/mTOR signaling pathway. When LY294002 was used to inhibit PI3K/AKT/mTOR signaling pathway, the effect of pcDNA3.1-SIK2 on aerobic glycolysis of breast cancer cells could be reversed. SIK2 can promote cisplatin resistance caused by aerobic glycolysis of breast cancer cells through PI3K/AKT/mTOR signaling pathway, which may be a new target to improve cisplatin resistance of breast cancer cells.

Clinical value of peripheral blood M2/M1 like monocyte ratio in the diagnosis of breast cancer and the differentiation between benign and malignant breast tumors.

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. In response to multiple microenvironmental signals from the tumor and stromal cells, macrophages change their functional phenotypes. Based on their function, macrophages are commonly classified into both, classical M1 and alternative M2 macrophages. M2-like tumor-associated macrophages promote breast tumor growth and survival, and may migrate into the peripheral blood. However, the level of circulating M2/M1-like monocyte ratio in the peripheral blood of breast cancer patients has not been yet clarified. To compare peripheral blood M2/M1 monocyte ratio among breast cancer patients, benign breast tumor patients and healthy subjects. Also, to investigate the role of peripheral blood M2/M1 monocyte ratio as a circulating breast cancer tumor marker and to asses the validity of this marker in differentiation between benign and malignant breast tumors. Flow cytometry technique was used to determine the peripheral blood M2/M1 monocyte ratio in three groups of subjects, i.e. 45 patients with breast cancer, 40 patients with benign breast tumor, and 40 healthy subjects as a control group. The results of carbohydrate antigen15-3 (CA15-3) determination were analyzed comparatively. The peripheral blood M2/M1 monocyte ratio in patients with breast cancer (0.27±0.1) was significantly higher (P<0.001) than that in healthy subjects (0.07±0.05) and than in benign tumor subjects (0.08±0.04). The area under the receiver operating characteristic (ROC) curve of peripheral blood M2/M1 monocyte ratio determination was significantly higher (P≤0.001) than that of CA15-3 levels. M2/M1-like monocyte ratio is of a high diagnostic value for breast cancer and is a promising differentiating marker between benign and breast cancer tumor groups.

Integrative transcriptome data mining for identification of core lncRNAs in breast cancer.

BackgroundCumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening.MethodsFirst, the linear fitting method was used to identify differentially expressed genes from the breast cancer RNA expression profiles in The Cancer Genome Atlas (TCGA). Next, the diagnostic value of all differentially expressed lncRNAs was evaluated using a receiver operating characteristic (ROC) curve. Then, the top ten lncRNAs with the highest diagnostic value were selected as core genes for clinical characteristics and prognosis analysis. Furthermore, core lncRNA-mRNA co-expression networks based on weighted gene co-expression network analysis (WGCNA) were constructed, and functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differential expression level and diagnostic value of core lncRNAs were further evaluated by using independent data set from Gene Expression Omnibus (GEO). Finally, the expression status and prognostic value of core lncRNAs in various tumors were analyzed based on Gene Expression Profiling Interactive Analysis (GEPIA).ResultsSeven core lncRNAs (LINC00478, PGM5-AS1, AL035610.1, MIR143HG, RP11-175K6.1, AC005550.4, and MIR497HG) have good single-factor diagnostic value for breast cancer. AC093850.2 has a prognostic value for breast cancer. AC005550.4 and MIR497HG can better distinguish breast cancer patients in early-stage from the advanced-stage. Low expression of MAGI2-AS3, LINC00478, AL035610.1, MIR143HG, and MIR145 may be associated with lymph node metastasis in breast cancer.ConclusionOur study provides candidate biomarkers for the diagnosis and prognosis of breast cancer, as well as a bioinformatics basis for the further elucidation of the molecular pathological mechanism of breast cancer.

Identification of five hub genes as monitoring biomarkersfor breast cancer metastasis in silico

BackgroundBreast cancer is one of the most common endocrine cancers among females worldwide. Distant metastasis of breast cancer is causing an increasing number of breast cancer-related deaths. However, the potential mechanisms of metastasis and candidate biomarkers remain to be further explored.ResultsThe gene expression profiles of GSE102484 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screen for the most potent gene modules associated with the metastatic risk of breast cancer, and a total of 12 modules were identified based on the analysis. In the most significant module (R2 = 0.68), 21 network hub genes (MM > 0.90) were retained for further analyses. Next, protein-protein interaction (PPI) networks were used to further explore the biomarkers with the most interactions in gene modules. According to the PPI networks, five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) were identified as key genes associated with breast cancer progression. Furthermore, the prognostic value and differential expression of these genes were validated based on data from The Cancer Genome Atlas (TCGA) and Kaplan-Meier (KM) Plotter. Receiver operating characteristic (ROC) curve analysis revealed that the mRNA expression levels of these five hub genes showed excellent diagnostic value for breast cancer and adjacent tissues. Moreover, these five hub genes were significantly associated with worse distant metastasis-free survival (DMFS) in the patient cohort based on KM Plotter.ConclusionFive hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) associated with the risk of distant metastasis were extracted for further research, which might be used as biomarkers to predict distant metastasis of breast cancer.

Radiomics Analysis of MRI for Predicting Molecular Subtypes of Breast Cancer in Young Women.

Breast cancer in young women is commonly aggressive, in part because the proportion of high-grade, triple-negative (TN) tumor is too high. There are certain limitations in the detection of biopsies or surgical specimens which only select part of tumor sample tissue and ignore the possible heterogeneity of tumors. In clinical practice, MRI is used for the diagnosis of breast cancer. MRI-based radiomics is a developing approach that may provide not only the diagnostic value for breast cancer but also the predictive or prognostic associations between the images and biological characteristics. In this work, we used radiomics methods to analyze MR images of breast cancer in 53 young women, and correlated the radiomics data with molecular subtypes. The results indicated a significant difference between TN type and non-TN type of breast cancer in young women on the radiomics features based on T2-weighted MR images. This may be helpful for the identification of TN type and guiding the therapeutic strategies.

Abstract P5-12-13: Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical therapy

Abstract To analyze the correlation of the level of serum heat shock protein 90α (HSP-90α) in healthy and breast cancer patients, studying the evaluation of neoadjuvant efficacy and Clinical value of relapse monitoring. A total of 102 healthy women were selected, 51 cases of breast benign tumor ,423 cases of female breast cancer all diagnosed by pathology,other system malignancies 62 cases. ALL the serum samples HSP-90αwas detected by double-antibody ELISA. The CEA, CA125,CA15-3 were detected by Roche Cobas ECL analyzer. The ROC curve was used to analyze the effectiveness of serum HSP-90α in the early diagnosis of breast cancer. The dynamic changes of HSP-90αlevel before and after treatment were analyzed by Wilcoxon's rank test. Moreover, we also combine the HSP-90αwith CEA,CA125,CA15-3 to evaluate the clinical value of monitoring the recurrence of breast cancer. The levels of serum HSP-90α (123.49 ± 105.1ng / ml) in breast cancer patients wes significantly higher than that in healthy controls (40.33 ± 14.18ng / ml), benign breast disease (80.15 ± 103.09ng / ml) and carcinoma in situ (34.7 ± (114.31 ± 146.91ng / ml),the difference was statistically significant (P &amp;lt;0.001). .According to the ROC curve analysis of patients and healthy subjects, the cut-offvalue was set as HSP-90=59.7ng / ml, AUC=0.834, the sensitivity and specificity to diagnosis of breast cancer was 90.3% and 78.6% respectively ,the negative predictive value was 93.88%.The levels of serum HSP-90α was significantly decreased (P &amp;lt;0.05) after tumor resection and the patients who obtain PR from the neoadjuvant chemotherapy. When HSP-90=43.22ng / ml was set as the cut-off value for diagnosing the recurrence of breast cancer, AUC=0.877,the sensitivity and specificity were 95.7% and 74.5% respectively, and the negative predictive value was 96.2%. At the same time, we find that combined HSP-90α with CEA, CA125, CA15-3 can improve the accuracy of recurrence prediction. Serum HSP-90α has a good clinical diagnostic value in breast cancer and can be used as a recurrence monitoring tool for post-adjuvant treatment patients. Citation Format: Hu N, Li M, Zhu A, Du F, Yuan P. Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-13.

The roles of ncRNAs in the diagnosis, prognosis and clinicopathological features of breast cancer: a systematic review and meta-analysis.

BackgroundA number of studies have shown that noncoding RNAs (ncRNAs) are abnormally expressed in breast cancers. However, the roles of ncRNAs remain unclear in breast cancer. Here, we aim to investigate the potential diagnostic and prognostic roles of ncRNAs in breast cancer.MethodsComprehensive literature search in Medline and Web of Science and a meta-analysis were performed to identify the association between ncRNAs and diagnosis, prognosis, and clinicopathological features of breast cancer.ResultsA total of 103 eligible studies, involving16, 828 independent participants, were included in the meta-analysis. In total, there were 98 individual and 11 grouped ncRNAs. 51 studies were eligible for survival analysis, 27 studies were eligible for diagnostic analysis, and 46 studies were eligible for clinicopathological features analysis. The abnormal expression of ncRNAs is associated with OS, RFS and PFS in breast cancer patients. For the diagnosis value of ncRNAs, the pooled OR and 95% CI for sensitivity, specificity, DOR and AUC on all ncRNAs were 0.83 [95% CI: 0.82- 0.84], 0.80 [95% CI: 0.79- 0.82], 24.77 [95% CI: 17.44- 35.16] and 0.9037, respectively. The analysis showed that downregulation of ncRNAs in breast cancer was associated with decreased risk of LNM, increased tumor size and PR expression, whereas, upregulation of ncRNAs was associated with increased HER2 expression.ConclusionsHigh expression of ncRNAs was associated with poor OS, RFS, and PFS, while low expression of ncRNAs was related to favorable OS and RFS. Meanwhile, ncRNAs have potential diagnostic value for breast cancer.

Combination of plasma HA and circulating M2-like monocytes may serve as a diagnostic marker for breast cancer.

Background: Breast cancer (BC)-derived hyaluronan (HA) can induce the formation of M2-like tumor-associated macrophages (TAMs) in tumor context. However, little is known about the correlation between circulating M2-like monocytes and plasma HA in BC patients. This study focused on evaluating the relationship between circulating M2-like monocytes and plasma HA, and further appraised the diagnostic value of them in BC.Methods: The expression of M2-like TAMs and HA was determined in pathological tissues by immunohistochemistry. Flow cytometry was used to detect the levels of circulating CD14+CD204+ M2-like monocytes in 81 BC patients, 45 patients with breast benign diseases, and 46 healthy subjects. The levels of HA, CEA, and CA15-3 were measured in plasma samples using chemiluminescence method.Results: M2-like TAMs and HA expressions were elevated in BC tissues compared with benign tissues. In correspondence, the frequency of circulating CD14+CD204+ M2-like monocytes and the plasma HA levels were significantly higher in patients with BC than those in control groups. Importantly, there was a positive correlation between circulating M2-like monocytes and the plasma HA (Spearman r = 0.404, p < 0.001). Area under receiver operating characteristic curve (ROC) for the combination of circulating M2-like monocytes and HA was 0.899 (95% CI: 0.853-0.946), which was higher than the panel of CEA and CA15-3.Conclusions: The frequency of circulating CD14+CD204+ M2-like monocytes was positively correlated to plasma HA levels. The combination of circulating CD14+CD204+ M2-like monocytes and plasma HA could provide considerable diagnostic value in BC.