Background Breast Cancer Research Articles

Development of graded prognostic assessment for breast Cancer brain metastasis incorporating extracranial metastatic features: a retrospective analysis of 284 patients

BackgroundBreast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM.MethodsThis study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models.Results284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and <0.001). Multivariate analysis demonstrated that molecular subtype, presence of ECM, and number of brain metastasis significantly influenced OS after BCBM. By modifying the current GPA model to include more precise characteristics of ECM, the predictive accuracy was further enhanced as indicated by the C-index and RMST curve.ConclusionsMore ECM sites, both bone and visceral invasion and uncontrolled ECM were dismal prognostic factors for survival outcomes of BCBM patients. A new Breast-GPA model with better predictive effect was constructed.

Validation of gene polymorphisms (rs2682818 and rs2043556) in has-miR-618 and has-miR-605 with the breast cancer susceptibility

BackgroundBreast cancer (BC) is one of the most frequent types of cancer and the second leading cause of cancer-affiliate death among ladies. BC is a heterogeneous sickness that is impacted by environment and genetic elements. Diagnosis in the early stages impacts treatment and patient survival rate. miRNA can play a vital role in BC's early stages of tumorigenesis. Single nucleotide polymorphism (SNP) can cause changes in miRNA expression and function, which are related to the risk of several cancers. AimThe goal of this examination is to assess the affiliation among two has-miR-605 (rs2043556A > G) and has-miR-618 (rs2682818 C > A) gene polymorphisms with the risk of BC in the Iranian ladies. MethodsOur case-control examination assessed two hundred whole blood samples of one hundred ladies with BC and one hundred healthy ladies. Hence, to assess the connection between the presence of SNP miRNA genes and the risk of BC, genotyping was done by the usage of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, then the usage of the Chi-square test of SPSS software statistically analyzed the acquired result. ResultsOur findings confirmed a statistically substantial distinction within the genotype frequency of the has-miR-618 gene polymorphism among the groups (P = 0.043), whereas no statistically substantial distinction inside the genotype frequency of the has-miR-605 gene polymorphism among the control and case (P = 0.183). In addition, the allelic frequency of two polymorphisms, (rs2043556 A > G) G allele (OR = 2.163, CI 95 % = 1.56–2.988, P = 0.022) and (rs2682818 C > A) A allele (OR = 3.997, CI 95 % = 1.584–10.081, P = 0.002) substantially enhance the risk of BC. ConclusionThe results show that the G allele of rs2043556 and the A allele of rs2682818 increase the risk of BC in the women population of East Azerbaijan province.

Plasma metabolomics profiles and breast cancer risk

BackgroundBreast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors.MethodsWe conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features.ResultsWe found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%.ConclusionsIf replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.

Systematic screening of protein-coding gene expression identified VWF as a potential key regulator in anthracycline-based chemotherapy-exacerbated metastasis of breast cancer

BackgroundBreast cancer is the most commonly diagnosed cancer worldwide. Although major treatments represented by chemotherapy have shown effectiveness at the initial period, recurrence and metastasis still occur later after treatments. The alternation of the tumor microenvironment by chemotherapy is confirmed as a trigger of the elevated proliferation and migration of the remaining tumor cells.MethodsUsing bioinformatic methods, differential gene expression analysis was used to determine DEGs between post-chemotherapy and pre-chemotherapy samples of breast cancer patients, followed by survival analysis and ELISA analysis of the potential key genes. An in vitro model of 2 breast cancer cells lines was used to demonstrate the role of VWF in the evasion and migration of breast cancer cells, using cell migration, evasion and wound healing assays, PCR and molecular docking analysis.Results19 hub genes were further identified using GO and KEGG pathway analyses and WGCNA. The 5 secreted protein-coding genes with reported carcinogenesis effects (VWF, SVEP1, DPT, ADIPOQ, and LPL) were further analyzed in breast cancer patients and VWF was identified as a potential key regulator in the anthracycline-based chemotherapy-exacerbated metastasis. It was further confirmed that anthracycline-based chemotherapeutics doxorubicin exacerbated VWF upregulation and the evasion and migration of breast cancer cells. Based on molecular docking analysis and previous study, berberine was used as an inhibitor of VWF, and showed an effective inhibition of the doxorubicin-exacerbated VWF upregulation, migration and evasion in breast cancer.ConclusionsDoxorubicin-exacerbated evasion and migration through VWF upregulation. Berberine as an inhibitor of VWF was able to reversed the doxorubicin-exacerbated VWF upregulation and evasion and migration in breast cancer cells.

CureMate: A clinical decision support system for breast cancer treatment

BackgroundBreast Cancer (BC) poses significant challenges in treatment decision-making. Multiple first treatment lines are currently available, determined by several patient-specific factors that need to be considered in the decision-making process. PurposeTo present CureMate, a Clinical Decision Support System to predict the most effective initial treatment for BC patients. Different artificial intelligence models based on demographic, anatomopathological and magnetic resonance imaging variables are studied. CureMate’s web application allows for easy use of the best model. MethodsA database of 232 BCE patients, each described by 29 variables, was established. Out of four machine learning algorithms, specifically Decision Tree Classifier (DTC), Gaussian Naïve Bayes (GNB), k-Nearest Neighbor (K-NN), and Support Vector Machine (SVM), the most suitable model for the task was identified, optimized and independently tested. ResultsSVM was identified as the best model for BC treatment planning, resulting in a test accuracy of 0.933. CureMate’s web application, including the SVM model, allows for introducing the relevant patient variables and displays the suggested first treatment step, as well as a diagram of the following steps. ConclusionThe results demonstrate CureMate’s high accuracy and effectiveness in clinical settings, indicating its potential to aid practitioners in making informed therapeutic decisions.

Advanced machine learning unveils CD8 + T cell genetic markers enhancing prognosis and immunotherapy efficacy in breast cancer

BackgroundBreast cancer (BC) is the most common cancer in women and poses a significant health burden, especially in China. Despite advances in diagnosis and treatment, patient variability and limited early detection contribute to poor outcomes. This study examines the role of CD8 + T cells in the tumor microenvironment to identify new biomarkers that improve prognosis and guide treatment strategies.MethodsCD8 + T-cell marker genes were identified using single-cell RNA sequencing (scRNA-seq), and a CD8 + T cell-related gene prognostic signature (CTRGPS) was developed using 10 machine-learning algorithms. The model was validated across seven independent public datasets from the GEO database. Clinical features and previously published signatures were also analyzed for comparison. The clinical applications of CTRGPS in biological function, immune microenvironment, and drug selection were explored, and the role of hub genes in BC progression was further investigated.ResultsWe identified 71 CD8 + T cell-related genes and developed the CTRGPS, which demonstrated significant prognostic value, with higher risk scores linked to poorer overall survival (OS). The model’s accuracy and robustness were confirmed through Kaplan-Meier and ROC curve analyses across multiple datasets. CTRGPS outperformed existing prognostic signatures and served as an independent prognostic factor. The role of the hub gene TTK in promoting malignant proliferation and migration of BC cells was validated.ConclusionThe CTRGPS enhances early diagnosis and treatment precision in BC, improving clinical outcomes. TTK, a key gene in the signature, shows promise as a therapeutic target, supporting the CTRGPS’s potential clinical utility.

The effect of web based and traditional self breast examination education on nursing students’ knowledge, skills and self-directed learning skills: A randomised controlled study

AimThe aim of this study is to examine the effect of web based self-breast examination education on nursing students’ knowledge, skills, and self-directed learning skills in self-breast examination. BackgroundBreast cancer is the most prevalent type of cancer among women, mortality rates are still high today. It is critical to improve the knowledge and skills and raise the self-awareness and health consciousness of individuals and society about self-breast examination, which is important in the early diagnosis of breast cancer, in order to lower mortality rates. Accordingly, one of the basic nursing skills aimed to be acquired by nursing students future nursing professionals is a self-breast examination. DesignThis study was conducted with a randomised, controlled, and experimental trial. MethodsA total of 90 students were included in the study: the intervention group (n=43) and the control group (n=47). Intervention group students participated in web-based SBE Education.Control group students participated in SBE Education based on a traditional learning model.A Student Information Form, the Self-Breast Examination Knowledge Test, the Self-Breast Examination Skill Rubric, and the Self-Directed Learning Skills Scale were used in the study. Descriptive statistics, Mann-Whitney U test, and Wilcoxon test were run to analyse the data. ResultsIt was observed that the control group had a higher score in self-breast examination knowledge than the intervention group during the intervention period and the follow-up period after 15 days. No difference was noticed between the groups after the intervention for self-breast examination skill score, but the intervention group had a higher score than the control group for self-breast examination skill during the follow-up period after 15 days. No significant difference was noted between the groups for self-directed learning scores. This result validated hypothesis H4. This result refuted hypothesis H1, H2, H3, H5. ConclusionsWeb based education on self-breast examination improves students’ breast self-examination skills and self-directed learning skills, but not their knowledge level of self-breast examination.

Pain neuroscience education and therapeutic exercise for the treatment of sequelae in breast cancer survivors living with chronic pain: A pilot study

BackgroundBreast cancer represents the most common type of malignant neoplasm worldwide. Advances in diagnosis and treatment have increased the life expectancy of patients. However, the sequelae associated with the treatment of the disease such as chronic pain, kinesiophobia and loss of physical function in breast cancer survivors (BCS) are a long-term health problem. Therapeutic strategies are required for the treatment of chronic sequelae in this population. ObjectivesTo evaluate the effectiveness of a pain neuroscience education (PNE) and therapeutic exercise (TE) for the treatment of chronic sequelae in BCS. MethodsQuasi-experimental repeated measures study. The intervention lasted 9 weeks, with 3 educational and 24 exercise sessions. Pain frequency and intensity (VAS scale), neuropathic pain (DN4), kinesiophobia level (TSK-11V), central sensitization (CSI-Sp), functionality of the affected arm (ULFI-Sp) and active joint range (ROM) with goniometry were measured at baseline, 3rd, 6th and 9th week. Statistical analysis included Friedman's test and ANOVA according to normality criteria. ResultsA total sample of 26 BCS participate in the study. Significant statistical changes were found from the 3rd week of treatment in the frequency and intensity of pain, kinesiophobia and neuropathic pain (p < 0.05). All variables had significant changes at the 9th week (p = 0.001). ConclusionThe results of the present investigation suggest that the combination of PNE and TE are effective in treating sequelae at short term in BCS with chronic pain.

Preliminary investigation on the mechanism of baicalein regulating the effects of Nischarin on invasion and apoptosis of human breast cancer cells MCF-7 through Wnt3α/β-catenin pathway

BackgroundBreast cancer (BC) remains the leading cause of cancer-related mortality in women. Here, we investigate the anti-tumor effects of baicalein on human BC cells (MCF-7 cells) and explore if it regulates the Nischarin protein via Wnt3α/β-catenin signaling pathway. MethodsWe employed Wnt3α and DKK-1 to activate and inhibit the Wnt/β-catenin signaling pathway, respectively. We used CCK-8 cell viability, flow cytometry apoptosis, wound-healing and transwell migration/invasion assays. Further, using western blotting and real-time quantitative PCR (q-PCR) we analyzed expression levels of Nischarin, MMP-9, Wnt/β-catenin pathway (β-catenin, Axin 1), and apoptotic pathway (Bax, Bcl-2) proteins and their mRNAs. ResultsWe found that baicalein inhibits MCF-7 cell viability and promotes apoptosis (evidenced by increased Bax and decreased Bcl-2 expressions) in a concentration-dependent manner. It also inhibits TPA-induced migration and invasion, and downregulates MMP-9 expression. Baicalein reverses the increase in cell viability caused by Wnt3α-induced Wnt/β-catenin pathway activation. Conversely, baicalein counteracts the increase in apoptosis caused by DKK-1 mediated inhibition of the Wnt/β-catenin pathway. Additionally, baicalein upregulates Nischarin expression via modulating the Wnt/β-catenin pathway as indicated by the antagonistic effects of Wnt3α and DKK-1 on this effect of baicalein. ConclusionBaicalein exerts anti-tumor effects on MCF-7 cells through the Wnt3α/β-catenin signaling pathway, and promotes apoptosis and inhibits migration and invasion. The upregulation of Nischarin by baicalein further suggests a potential therapeutic target for BC treatment.

Global, regional, and national trends in the burden of breast cancer among individuals aged 70 years and older from 1990 to 2021: an analysis based on the global burden of disease study 2021

BackgroundBreast cancer poses a substantial health challenge for the world’s over-70 population. However, data on the impact and epidemiology of breast cancer in this age group are limited. We aimed to evaluate global, regional, and national breast cancer trends among those aged 70 and older between 1990 and 2021.MethodsIn this trend analysis based on the 2021 Global Burden of Diseases (GBD), we report on the incidence rates and Global Burden of Diseases (GBD) disability-adjusted life years (DALYs) counts, as well as the incidence rates per 100,000 individuals and average annual percentage changes (AAPCs) for breast cancer among individuals aged 70 and above at the global, regional, and national levels. We analyzed these global trends by age, sex, and socio-developmental index (SDI). Joinpoint regression elucidates pivotal trend shifts.ResultsFrom 1990 to 2021, the global incidence of breast cancer in the over-70 population modestly increased from 104 to 107 per 100,000, with significant trend changes in 1995, 2005, and 2018. Regionally, High-income North America had the highest incidence in 2021, while North Africa and the Middle East saw the steepest rise in incidence and DALYs. The only decrease was in the High SDI quintile. The 70–74 age group experienced the largest increase globally, with rates rising from 86.3 to 90 per 100,000 (AAPC 0.27).ConclusionFrom 1990 to 2021, global breast cancer incidence in the over-70 population saw a slight uptick, contrasted by a significant reduction in DALYs, likely due to progress in endocrine and targeted therapies. This underscores the critical need for enhanced screening and personalized treatments for older patients.

I trust doctors and midwives: exploring breast cancer literacy among women referring to the health centers in Iran

BackgroundBreast cancer (BC) is the most common cancer in women worldwide. Early diagnosis of BC could considerably improve outcomes. Since health literacy could influence preventive behaviors and women’s ability to make decisions about breast care, therefore, this study aimed to explore breast cancer literacy in women.MethodsThis qualitative study was conducted in Iran using the directed content analysis. Data were collected through face-to-face interviews with a purposeful sample of women from April 2021 to June 2022 and continued until saturation was reached. Interviews were analyzed using the initial matrix developed based on the European health literacy framework.ResultsIn all twelve women were interviewed. During data analysis, 612 primary codes grouped into four dimension of health literacy (access, understanding, appraise, and apply) of three health domain (health care, disease prevention, and health promotion). Many believed that it was difficult to access accurate information about BC. They used various sources to obtain information. The participants addressed some facilitators and barriers in understanding the information and for information appraisal they mentioned seeking help from health professionals. Through the acquired cognitive skills, the participants took some steps to apply BC information. Also, having information about BC and the involvement of relatives with cancer were indicated as triggers for decision-making on breast care, while poor financial conditions, not having enough information, fear, shame, and embarrassment, were pointed out as inhibiting factors.ConclusionsThe findings suggest that barriers in access, and understanding of information on breast cancer exist among women. The findings also suggest that women’s decision-making and preventive behaviors on breast care are much dependent on social and cultural factors.

Does the use of Acellular Dermal Matrices (ADM) in women undergoing pre-pectoral implant-based breast reconstruction increase operative success versus non-use of ADM in the same setting? A systematic review

BackgroundBreast cancer is the most common malignancy among women in the UK. Reconstruction – of which implant-based breast reconstruction (IBBR) is the most common – forms a core part of surgical management of breast cancer. More recently, pre-pectoral IBBR has become common as technology and operative techniques have evolved. Many surgeons use acellular dermal matrix (ADM) in reconstruction however there is little evidence in literature that this improves surgical outcomes. This review will assess available evidence for surgical outcomes for breast reconstructions using ADM versus non-use of ADM.MethodsA database search was performed of Ovid Medline, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (2012–2022). Studies were screened using inclusion and exclusion criteria. Risk of Bias was assessed using the Newcastle Ottawa scale and ROBIS tools. Analysis and meta-analysis were performed.ResultsThis review included 22 studies (3822 breast reconstructions). No significant difference between overall complications and failure rates between ADM and non-ADM use was demonstrated. Capsular contracture, wound dehiscence and implant rippling had significant differences however these results demonstrated high heterogeneity thus wider generalisation may be inaccurate. Patient quality of life scores were not recorded consistently or comparably between papers.ConclusionsThis review suggests a lack of significant differences in most complications between ADM use and non-use for pre-pectoral IBBR. If no increase in complications exists between groups, this has significant implications for surgical and legislative decision-making. There is, however, inadequate evidence available on the topic and further research is required.

Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers

BackgroundBreast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive.MethodsIn this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities.ResultsWe observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy.ConclusionsOur findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Breast cancer molecular subtype classification according to immunohistochemistry markers and its association with pathological characteristics among women attending tertiary hospitals in Tanzania

BackgroundBreast cancer immunohistochemistry is a biological characteristic of the tumour which has a role to diagnose molecular subtype, prognosticate and guide treatment and is categorised into 4 subtypes. Data in Tanzania was lacking and was based off data extrapolated from studies in Western Africa thus hypothesizing that women of African ancestry predominately develop Triple Negative Breast Cancer (TNBC). MethodsA retrospective cross-sectional study was carried out at two tertiary referral hospitals on participants who were recruited from the cancer registries from 2015 to 2022. Prevalence of each molecular subtype was determined and association between molecular subtype to demographic and pathological characteristics were evaluated. Predictors of molecular subtypes was then determined using logistic regression. ResultsTotal number of participants were 1214, median age was 50 (IQR: 41–61), median tumor size was 5 cm (IQR: 4–7) with lymph node positivity in 73.7 %. Immunohistochemistry studies showed estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) receptor positivity in 54.4 %, 34.4 % and 27.8 % of cases respectively. Molecular subtype classification prevalence for Luminal A was 21.17 % (95 % CI: 18.87–23.47), for Luminal B 35.75 % (95 % CI: 33.05–38.45), for HER2 enriched 11.86 % (95 % CI: 10.04–13.68) and for TNBC 31.22 % (95 % CI: 28.61–33.83). Significant association was seen between molecular subtype with age, tumor size, tumor grade and lymph node involvement. Predictors of Luminal tumors were larger tumor size (aOR 1.217, 95 % CI: 1.149–1.291) no lymph node involvement (aOR 0.429, 95 % CI: 0.313–0.589) while an advanced tumor grade reduced likelihood (aOR 0.041, 95 % CI: 0.011–0.019). ConclusionIn Tanzania Luminal B was most predominant subtype presenting at an earlier age and associated with more favorable pathological characteristics.

Expression of Axl Receptor Tyrosine Kinase and Its Association With Ki-67 Proliferation Marker, BCL-2 Anti-apoptotic Protein, Hormone Receptor Status, and HER2/Neu Status in Breast Cancer Among Women From Duhok, Iraq.

Background Breast cancer (BC) is the most prevalent cancer among women worldwide, contributing to high mortality rates, especially in Iraqi women. Detecting the disease before metastasis may increase survival chances for many patients, but that is not the case for most of them. Thus the search for new prognostic biomarkers or testing the relevance of existing ones could contribute to therapeutic decisions complementing the traditional methods, including TNM (tumor, node, and metastasis) staging, tumor grade, and other clinicopathological features in addition to the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). The Axl receptor is frequently associated with invasion, migration, poor prognosis, and angiogenesis. Furthermore, its association with chemotherapyand targeted therapy resistance makes itan ideal biomarker for therapeutic targeting. Methodology This study involved 50 malignant cases with 25 benign fibroadenoma and non-neoplastic cases represented by inflammatory conditions, collected with their corresponding data from the central lab in Duhok Governorate, Iraq. Expression of Kiel 67 (Ki-67) proliferation marker and B-cell lymphoma 2 (BCL-2) anti-apoptotic protein was measured using immunohistochemistry (IHC) to estimate tumor growth and apoptosis. Gene expression of the Axl receptor was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Cases with high Ki-67 accounted for 68% and low Ki-67 cases were 32% across the graded groups and were significantly associated with tumor grade, PR, and HER2. BCL-2-negativecases accounted for 62% and BCL-2-positive cases were 38%. It was revealed that BCL-2 had a strong correlation with age, especially inthose under 50 years.As for the Axl gene expression, the average fold change in expression in the high-grade (H.) group was 1.74 times higher than in the control group, while in the low/intermediate (L.) group, it was 3.74 times higher. Additionally, when comparing these results with other variables, no significant associations were observed. Conclusion Axl receptor was not associated with all of the clinicopathological variables, the expression values were high in malignant tumors in comparison with the benign tumors, and it was found that Axl receptor expression was associated with low/intermediate grade, which is considered a favorable prognostic factor. Although Axl receptor expression was previously linked with proliferation and invasiveness in BC, its association with the Ki-67 proliferation marker and BCL-2 anti-apoptotic protein was not observed.

MIR4435-2HG: A novel biomarker for triple-negative breast cancer diagnosis and prognosis, activating cancer-associated fibroblasts and driving tumor invasion through EMT associated with JNK/c-Jun and p38 MAPK signaling pathway activation

BackgroundBreast cancer has the highest incidence rate and causes the most fatalities among all female cancers worldwide. Triple-negative breast cancer (TNBC) is known for its strong invasiveness and higher rates of recurrence. In this research, we aimed to identify MIR4435-2HG as a promising long non-coding RNA (lncRNA) biomarker and therapeutic target for TNBC. MethodsUtilizing clinicopathological information and transcriptome data from The Cancer Genome Atlas (TCGA) database, we assessed the clinical relevance of MIR4435-2HG in breast cancer through univariate and multivariate COX regression, receiver operating characteristic (ROC) analysis, as well as Kaplan-Meier survival analysis. To investigate the biological role of MIR4435-2HG in TNBC, we conducted gene set enrichment analysis (GSEA), as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, we constructed and validated a nomogram to predict disease-free survival (DFS). Both the R package “pRRophetic” and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were employed to forecast the sensitivity to different therapeutics between the high- and low-MIR4435-2HG groups. We employed single-cell RNA sequencing analysis and tumor microenvironment infiltration analysis to investigate the potential involvement of MIR4435-2HG in the TNBC tumor microenvironment. Cellular biological behaviors were assessed utilizing CCK-8, transwell assays, and wound-healing assays. Furthermore, we performed RNA-seq, qRT-PCR, and western blotting analyses to elucidate and confirm the specific mechanisms underlying the role of MIR4435-2HG in TNBC. ResultsIn our study, we have identified MIR4435-2HG as a significant diagnostic and prognostic factor for TNBC. We observed that MIR4435-2HG is widely expressed and might have a significant impact on the reshaping of the TNBC tumor microenvironment. Patients with TNBC in the high-MIR4435-2HG group may show reduced sensitivity to cisplatin, doxorubicin, and gemcitabine and have an increased propensity for immune escape. Knockdown of MIR4435-2HG inhibits cancer-associated fibroblasts (CAFs) activation. Notably, MIR4435-2HG predominantly enhances the migratory and invasive capabilities of TNBC cells through the epithelial-mesenchymal transition (EMT) process. Mechanistically, we validated that MIR4435-2HG activates the JNK/c-Jun and p38 non-classical MAPK signaling pathway in TNBC cells. ConclusionsOur findings highlight the significant potential of MIR4435-2HG as a highly promising biomarker for TNBC. Targeting MIR4435-2HG could represent an appealing therapeutic approach for TNBC.

A hybrid features fusion-based framework for classification of breast micronodules using ultrasonography

BackgroundBreast cancer is one of the leading diseases worldwide. According to estimates by the National Breast Cancer Foundation, over 42,000 women are expected to die from this disease in 2024.ObjectiveThe prognosis of breast cancer depends on the early detection of breast micronodules and the ability to distinguish benign from malignant lesions. Ultrasonography is a crucial radiological imaging technique for diagnosing the illness because it allows for biopsy and lesion characterization. The user’s level of experience and knowledge is vital since ultrasonographic diagnosis relies on the practitioner’s expertise. Furthermore, computer-aided technologies significantly contribute by potentially reducing the workload of radiologists and enhancing their expertise, especially when combined with a large patient volume in a hospital setting.MethodThis work describes the development of a hybrid CNN system for diagnosing benign and malignant breast cancer lesions. The models InceptionV3 and MobileNetV2 serve as the foundation for the hybrid framework. Features from these models are extracted and concatenated individually, resulting in a larger feature set. Finally, various classifiers are applied for the classification task.ResultsThe model achieved the best results using the softmax classifier, with an accuracy of over 95%.ConclusionComputer-aided diagnosis greatly assists radiologists and reduces their workload. Therefore, this research can serve as a foundation for other researchers to build clinical solutions.

Serum exosomal miR-200c is a potential diagnostic biomarker for breast cancer

Background Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in BC serum exosomes and its diagnostic value. Methodology miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7, MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves. Results We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without BC disease and could be used as an early diagnostic marker for BC disease. Conclusion Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.

Anoikis-related genes in breast cancer patients: reliable biomarker of prognosis

BackgroundBreast cancer (BC) is the most common cancer in women, and its progression is closely related to the phenomenon of anoikis. Anoikis, the specific programmed death resulting from a lack of contact between cells and the extracellular matrix, has recently been recognized as playing a critical role in tumor initiation, maintenance, and treatment. The ability of cancer cells to resist anoikis leads to cancer progression and metastatic colonization. However, the impact of anoikis on the prognosis of BC patients remains unclear.MethodThis study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect transcriptome and clinical data of BC patients. Anoikis-related genes (ARGs) were classified into subtypes A and B through consensus clustering. Subsequently, survival prognosis analysis, immune cell infiltration analysis, and functional enrichment analysis were performed for both subtypes. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a set of 10 ARGs related to prognosis was identified. Immune cell infiltration and tumor microenvironment analyses were conducted on these 10 ARGs to develop a prognostic model. Furthermore, single-cell data analysis and real-time polymerase chain reaction (RT-PCR) analysis were employed to study the expression of the 10 identified prognostic ARGs in BC cells.ResultsOne hundred thirty-five ARGs were identified as differentially expressed genes in the TCGA and GEO databases, with 42 of them associated with the survival prognosis of BC patients. Analyses involving Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), and Uniform Manifold Approximation and Projection (UMAP) revealed distinct expression patterns of ARGs between types A and B. Patients in type A exhibited worse survival prognosis and lower immune cell infiltration compared to type B. Subsequent analyses identified 10 key ARGs (YAP1, PIK3R1, BAK1, PHLDA2, EDA2R, LAMB3, CD24, SLC2A1, CDC25C, and SLC39A6) relevant to BC prognosis. Kaplan–Meier analysis indicated that high-risk patients based on these ARGs had a poorer BC prognosis. Additionally, Cox regression analysis established gender, age, T (tumor), N (nodes), and risk score as predictive factors in a nomogram model for BC. The model demonstrated diagnostic value for BC patients at 1, 3, and 5 years. Decision curve analysis (DCA) verified the risk score as a reliable predictor of BC patient survival rates. Moreover, RT-PCR results confirmed differential expressions of YAP1, PIK3R1, BAK1, PHLDA2, CD24, SLC2A1, and CDC25C in BC cells, with SLC39A6, EDA2R, and LAMB3 showing low expression levels.ConclusionARGs markers can be used as BC biomarkers for risk stratification and survival prediction in BC patients. Besides, ARGs can be used as stratification factors for individualized and precise treatment of BC patients.

ZFP64 drives glycolysis-mediated stem cell-like properties and tumorigenesis in breast cancer

BackgroundBreast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway.ResultsIt was demonstrated that ZFP64 was overexpressed in BC specimens compared to adjacent normal tissues, and patients with high ZFP64 expression had shorter overall survival and disease-free survival. The analysis of the association of ZFP64 expression with clinicopathological characteristics showed that high ZFP64 expression is closely associated with N stage, TNM stage, and progesterone receptor status. Knockdown of ZFP64 suppressed the viability and colony formation capacity of BC cells by CCK8 and colony formation assays. The subcutaneous xenograft models revealed that ZFP64 knockdown reduced the volume of formatted tumors, and decreased Ki67 expression in tumors. The opposite effects on cell proliferation and tumorigenesis were demonstrated by ZFP64 overexpression. Furthermore, we suggested that the stem cell-like properties of BC cells were inhibited by ZFP64 depletion, as evidenced by the decreased size and number of formatted mammospheres, the downregulated expressions of OCT4, Nanog, and SOX2 proteins, as well as the reduced proportion of CD44+/CD24− subpopulations. Mechanistically, glycolysis was revealed to mediate the effect of ZFP64 using mRNA-seq analysis. Results showed that ZFP64 knockdown blocked the glycolytic process, as indicated by decreasing glycolytic metabolites, inhibiting glucose consumption, and reducing lactate and ATP production. As a transcription factor, we identified that ZFP64 was directly bound to the promoters of glycolysis-related genes (ALDOC, ENO2, HK2, and SPAG4), and induced the transcription of these genes by ChIP and dual-luciferase reporter assays. Blocking the glycolytic pathway by the inhibition of glycolytic enzymes ENO2/HK2 suppressed the high proliferation and stem cell-like properties of BC cells induced by ZFP64 overexpression.ConclusionsThese data support that ZFP64 promotes stem cell-like properties and tumorigenesis of BC by activating glycolysis in a transcriptional mechanism.