Breast Cancer Research最新文献

{"title":"Wearable device for axillary lymph node screening in breast cancer based on infrared thermography and artificial intelligence.","authors":"Xiaoying Zhong, Jinqiu Deng, Ping Lu, Zhichao Zuo, Yu Zhao, Yidong Zhou, Xuefei Wang","doi":"10.1186/s13058-025-02027-4","DOIUrl":"https://doi.org/10.1186/s13058-025-02027-4","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most prevalent cancer among women worldwide, and patients with metastasis to axillary lymph nodes (ALN) experience significantly lower survival rates. Current imaging-based screening methods often suffer from low sensitivity and limited accessibility for detecting ALN metastasis in breast cancer patients. In this study, we present an AI-based infrared thermography system for ALN metastasis detection to improve diagnostic accessibility and reduce intervention-related morbidity.</p><p><strong>Methods: </strong>In this study, we curated an internal and external cohort for developing and accessing the deep learning model-based infrared thermography system. The internal cohort included 460 inpatient participants from Peking Union Medical College Hospital, randomly divided into a training set (70%) for model development and a hold-out internal validation set (30%) for initially model evaluation. The external cohort, consisting of 80 patients from both outpatient and inpatient departments recruited from Longfu Hospital, served for independent validation of the developed screening tool.</p><p><strong>Results: </strong>The developed model AI-IRT for axillary lymph node (ALN) metastasis detection exhibited high diagnostic performance, achieving an Area Under the Curve (AUC) of 0.9424 and an accuracy of 0.8478 in the internal validation set, with a sensitivity of 0.8958 and specificity of 0.8222. In a tertiary classification scenario, the model produced an AUC of 0.8936, with corresponding accuracy, sensitivity, and specificity values of 0.7246, 0.7246, and 0.7852, respectively. In the external validation set, the AI-IRT system achieved an AUC of 0.881 and an accuracy of 0.875, with a sensitivity of 0.892 and specificity of 0.861. For the tertiary classification, the model attained an AUC of 0.771 and an accuracy of 0.613, with both sensitivity and specificity at 0.613 and 0.695, respectively.</p><p><strong>Conclusion: </strong>Evaluated on both curated internal and external cohorts, the proposed AI-IRT demonstrated strong performance across multiple centers, highlighting its potential to enhance pre-operative and intra-operative decision-making in the treatment of breast cancer patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"104"},"PeriodicalIF":7.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of adjuvant bone modifying agent use in patients with early-stage breast cancer in the United States.","authors":"Nicole Odzer, Rachel Jaber Chehayeb, Sarah E Schellhorn, Maryam Lustberg, Cary P Gross, Do Lee, Julia Foldi","doi":"10.1186/s13058-025-02062-1","DOIUrl":"10.1186/s13058-025-02062-1","url":null,"abstract":"<p><strong>Purpose: </strong>Based on improved survival, the 2017 ASCO and Cancer Care Ontario clinical guidelines (ACGD) recommended consideration of adjuvant bisphosphonates for postmenopausal women with early-stage breast cancer (EBC). However, small survey-based studies suggest inconsistent prescribing. This study evaluated receipt of adjuvant bone modifying agents (BMAs) in the United States before and after publication of the 2017 ACGD.</p><p><strong>Methods: </strong>This nationwide retrospective cohort study used a deidentified electronic health record-derived database to identify patients diagnosed with stage I-III EBC treated at health care practices from 2012 to 2019. We defined adjuvant BMA (bisphosphonates or denosumab) use as first dose received within 24 months of EBC diagnosis. We used Chi-squared and multivariable logistic regression analyses to compare the proportion of patients receiving adjuvant BMAs pre- and post-ACGD and identify factors associated with receipt of any BMA as well as bisphosphonates alone.</p><p><strong>Results: </strong>Our cohort included 11,470 patients. Most patients were 50 years of age or older (82%), and had stage I (57%), node-negative (70%) and estrogen receptor (ER)-positive (76%) breast cancer. Patients diagnosed post-ACGD (2017-19) were more likely to receive adjuvant BMAs (9%) than patients diagnosed in earlier years (7.4%; odds ratio [OR] 1.23; 95% confidence interval (CI) 1.08-1.42; p = 0.002). Post-menopausal status, age ≥ 50, receipt of adjuvant chemotherapy and endocrine therapy, and coexisting bone loss diagnoses were significantly associated with increased receipt of adjuvant BMAs. Among BMA recipients, 65.8% received denosumab only, 32.6% received bisphosphonates only, and 1.4% received both.</p><p><strong>Conclusions: </strong>Even after release of the ACGD guidelines, adjuvant BMA prescribing was low, and the majority of patients who received BMA did not receive bisphosphonates.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"102"},"PeriodicalIF":7.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation patterns in breast cancer, paired benign tissue from ipsilateral and contralateral breast, and healthy controls.","authors":"Saya R Dennis, Takahiro Tsukioki, Gannon Cottone, Wanding Zhou, Patricia A Ganz, Mary E Sehl, Yuan Luo, Seema A Khan, Susan Clare","doi":"10.1186/s13058-025-02057-y","DOIUrl":"10.1186/s13058-025-02057-y","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic changes, particularly DNA methylation, are crucial to breast cancer development. Tumor-adjacent normal (AN) tissue frequently serves as a reference for characterizing genomic alterations but is reported to share some characteristics with tumors. However, it is unclear whether AN's epigenetic profiles reflect a predisposition to cancer or a response to the presence of the tumor. We address this gap by systematically comparing methylation profiles of tumor, AN, and matched-benign tissues from both breasts, as well as to healthy donated breast tissue.</p><p><strong>Methods: </strong>We studied four different sample categories from 69 cancer cases: tumor (TU), AN, ipsilateral opposite quadrant (OQ), and contralateral unaffected breast (CUB); and healthy donated breast (HDB) tissue from 182 cancer-unaffected donors. These constitute a \"tumor proximity axis\" (TPxA): HDB→CUB→OQ→AN→TU. Methylation profiles were assayed using Illumina's Infinium Methylation EPICv1.0 BeadChip. Differential methylation (DM) analysis was conducted, and the significantly DM CpGs were analyzed for enrichment of transcription factor binding sites (TFBS) and other features.</p><p><strong>Results: </strong>Following data processing and quality control, there were 69 TU, 60 AN, 67 OQ, 68 CUB, and 182 HDB samples for analysis. DM analysis showed distinct methylation profiles of TU relative to benign tissues, whereas case-benign tissues were similar to each other but distinct from HDB. Hypomethylated sites in case-benign versus HDB were enriched for TF binding sites of TP63, GATA3, ESR1, PR, AR, NR3C1, and GREB1. TU hypermethylation events were enriched for Polycomb-repressive complex 2 (PRC2) binding, including EZH2, SUZ12, and JARID2, with hypermethylation enrichment for PRC2-related binding motifs in both ER + and ER- tumors. TU methylation profiles were otherwise highly distinct by ER status: TFBS enrichment of hypomethylation events for hormone receptor-related pathways in ER + tumors and for hematopoiesis/immune-related pathways in ER- tumors. We found no differential methylation between benign tissues from patients with ER + vs. ER- tumors.</p><p><strong>Conclusions: </strong>DNA methylation profiles differ profoundly at two points: tumor to case-benign and case-benign to HDB, with clear distinction between ER + and ER- tumors. Case-benign tissues are not epigenetically \"normal\", are similar across both breasts, and do not differ by ER status of paired tumors.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"103"},"PeriodicalIF":7.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the tumor microenvironment in primary breast angiosarcoma: insights from single-cell RNA sequencing.","authors":"Peikai Ding, Shengbin Pei, Yi Zhai, Zheng Qu, Yazhe Yang, Xiaolong Feng, Qiang Liu, Xiangyu Wang, Wenxiang Zhang, Zhongzhao Wang, Xiangyi Kong, Jing Wang, Yi Fang","doi":"10.1186/s13058-025-02022-9","DOIUrl":"10.1186/s13058-025-02022-9","url":null,"abstract":"<p><strong>Background: </strong>Angiosarcoma, a rare and highly aggressive malignancy originating from vascular endothelial cells, is characterized by its rapid progression, high invasiveness, and poor prognosis. Due to the limited understanding of its tumor microenvironment (TME) and the absence of effective treatments, further research is essential to elucidate its pathogenic mechanisms and improve therapeutic strategies.</p><p><strong>Objective: </strong>This study aims to characterize the cellular heterogeneity and unique TME of primary breast angiosarcoma using single-cell RNA sequencing (scRNA-seq), to identify potential therapeutic targets and improve clinical outcomes.</p><p><strong>Methods: </strong>Tumor samples were obtained from a patient with bilateral primary breast angiosarcoma and two patients with invasive breast cancer. Single-cell RNA sequencing (scRNA-seq) was conducted to capture the transcriptomic profiles of individual cells within the tumor samples. Following stringent quality control, a total of 31,771 cells were analyzed using comprehensive bioinformatics approaches. Cell populations were identified and classified into distinct cell types, and differential gene expression analysis was performed to explore key signaling pathways. Functional enrichment analysis was used to identify pathways related to tumor progression and immune evasion. Additionally, cell-cell communication networks were mapped to understand interactions within the TME, with a focus on pathways that may serve as therapeutic targets.</p><p><strong>Results: </strong>The scRNA-seq analysis revealed significant differences in the distribution of perivascular cells, fibroblasts, T cells, endothelial cells, and myeloid cells in breast angiosarcoma compared to invasive breast cancer. Key pathways enriched in angiosarcoma samples included growth factor binding, platelet-derived growth factor binding, and ribosome biogenesis, with abnormal expression of several ribosomal proteins. Notably, genes such as FAT4, KDR, FN1, and KIT were highly expressed in angiosarcoma endothelial cells, correlating with poor prognosis. Cell communication analysis highlighted the CXCL12-CXCR4 axis as a crucial mediator of the TME in angiosarcoma.</p><p><strong>Conclusion: </strong>This study provides critical insights into the TME of primary breast angiosarcoma, highlighting potential molecular targets and pathways for therapeutic intervention. These findings may inform the development of more effective treatment strategies for this rare and challenging tumor type.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"101"},"PeriodicalIF":7.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SENP5 drives breast cancer progression through deSUMOYlation of CDK1.","authors":"Cui Chen, Hanming Yao, Haiqing Jie, Zhenkang Liang, Yuxuan Zhang, Xinyun Wen, Jinze Zhao, Huiping Xiong, Zongheng Zheng, Juekun Wu","doi":"10.1186/s13058-025-02054-1","DOIUrl":"10.1186/s13058-025-02054-1","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) remains a significant global health concern, with the need for novel therapeutic targets to improve patient outcomes. The role of the SENP family of de-SUMOylating enzymes in BRCA is not yet fully understood.</p><p><strong>Methods: </strong>The expression and prognostic value of SENP family in BRCA were analyzed using the TCGA database. GSEA was conducted to identify correlations between SENP5 expression and cell cycle pathways. Experiments including Western blotting, RT-qPCR, CCK8 assays, colony formation assays, EdU staining, wound healing assays, and transwell assays were used to assess the impact of SENP5 knockdown on BRCA cell proliferation, migration, and invasion. Co-immunoprecipitation and fluorescence co-localization studies were employed to investigate the interaction between SENP5 and CDK1. The effects of combining SENP5 knockdown with CDK1 inhibition were evaluated in MDA-MB-231 xenograft mouse model.</p><p><strong>Results: </strong>SENP5 was found to be overexpressed in BRCA and associated with poor prognosis. Knockdown of SENP5 significantly inhibited BRCA cell proliferation and migration. GSEA revealed a strong correlation between SENP5 and the cell cycle, particularly the G2M checkpoint and E2F target pathways. SENP5 was shown to promote cell cycle progression by upregulating CDK1. Mechanistically, SENP5 mediates the de-SUMOylation of CDK1, reducing its degradation via the ubiquitin-proteasome pathway and increasing CDK1 expression. In vivo, the combination of SENP5 knockdown and CDK1 inhibition significantly suppressed BRCA tumor growth.</p><p><strong>Conclusion: </strong>Our research identifies the SENP5/CDK1 axis as a key player in BRCA progression, highlighting its potential as a therapeutic target.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"100"},"PeriodicalIF":7.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Methylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer.","authors":"Marie-Julie Nokin, Justine Bellier, Florence Durieux, Olivier Peulen, Gilles Rademaker, Maude Gabriel, Christine Monseur, Benoit Charloteaux, Lieven Verbeke, Steven van Laere, Patrick Roncarati, Michael Herfs, Charles Lambert, Jean Scheijen, Casper Schalkwijk, Alain Colige, Jo Caers, Philippe Delvenne, Andrei Turtoi, Vincent Castronovo, Akeila Bellahcène","doi":"10.1186/s13058-025-02044-3","DOIUrl":"10.1186/s13058-025-02044-3","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"99"},"PeriodicalIF":7.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in CTC and ctDNA detection techniques: opportunities for improving breast cancer care.","authors":"Hai-Jing Zhong, Yumiao Zhen, Shiji Chen, Wei Shi, Xiaoxu Liang, Guan-Jun Yang","doi":"10.1186/s13058-025-02024-7","DOIUrl":"10.1186/s13058-025-02024-7","url":null,"abstract":"<p><p>The advent of precision therapy has revolutionized breast cancer treatment, driven by the development of innovative diagnostic techniques and targeted drugs. Identifying biomarkers related to therapy response is crucial for tailoring treatment strategies for breast cancer patients. Liquid biopsies have emerged as minimally invasive techniques for biomarker profiling, leveraging the increasing sensitivity for detecting oncogenic drivers. These liquid biopsy methods, involving the testing of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in biofluids, offer more opportunities for early cancer detection, monitoring treatment efficacy, and identifying resistance mechanisms. This review focuses on the technical methodologies employed for the detection of CTCs and ctDNA. Beyond the technical aspects, we discuss the clinical applications of these biomarkers in breast cancer, including their roles in early detection, monitoring treatment response, and guiding therapeutic decisions. We also address the challenges associated with CTC and ctDNA detection, such as low concentrations in biofluids and tumor heterogeneity, which can complicate analysis and interpretation. By discussing the current landscape of CTC and ctDNA methodologies and their clinical implications, this review highlights the potential of liquid biopsies to enhance personalized medicine approaches in breast cancer management.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"97"},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialylated IgG expressed in triple-negative breast cancer cells promotes cancer progression by promoting glycolysis.","authors":"Chenyang Hu, Shenghua Zhang, Fugang Duan, Xinmei Huang, Jing Huang, Zhu Zhu, Xiaoning Mo, Weiyan Xu, Lina Wu, Zhimin Fan, Xiaoyan Qiu","doi":"10.1186/s13058-025-02052-3","DOIUrl":"10.1186/s13058-025-02052-3","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is among the most aggressive and lethal subtypes of breast cancer. To date, there are no effective targeted treatment targets. Sialylated IgG (SIA-IgG), with unique sialylated modifications for N-glycosylation at site 162 of the heavy chain of IgG, which was found to be expressed in a variety of cancer cells as a novel procancer factor. Here, we aimed to investigate the expression frequency and procancer mechanisms of SIA-IgG in TNBC, and determine whether the SIA-IgG is a key factor that promotes TNBC and a novel target for TNBC therapy.</p><p><strong>Methods: </strong>Immunohistochemical staining, immunofluorescence, and TCGA database analysis were performed to analyze the frequency of SIA-IgG expression in TNBC and the correlation between SIA-IgG expression and patient prognosis. Colony formation, transwell, and Matrigel-transwell assays were used to assess the proliferative and invasive abilities of SIA-IgG. Proteomic mass spectrometry and immunoprecipitation were utilized to identify the key procancer mechanisms of SIA-IgG. Oxygen consumption and extracellular acidification assays were used to elucidate the promotion of glucose metabolism and its mechanism in TNBC. Subcutaneous xenograft models were established to examine the antitumour effects of targeting SIA-IgG.</p><p><strong>Results: </strong>SIA-IgG was frequently detected in TNBC cells and was negatively associated with prognosis. Moreover, exogenously added SIA-IgG significantly enhanced the proliferation, migration and invasion of TNBC cells. Importantly, SIA-IgG significantly promoted TNBC progression by accelerating glycolysis and lactate reuse, which was dependent on its unique N-glycosylation at the Asn162 site. Conversely, the inhibition of SIA-IgG inhibited cancer cell proliferation and invasion by decreasing ATP and lactate production. Knockdown of SIA-IgG, as well as treatment with the anti-SIA-IgG antibody, significantly inhibited TNBC growth in vivo. Mechanistically, SIA-IgG promoted glycolysis and the lactate cycle mainly through the activation of two pathways: the integrin α6β4-FAK-AKT-HIF-1α-MCT4 axis, and the integrin α6β4-CD44-MCT1 axis.</p><p><strong>Conclusions: </strong>These findings suggest that SIA-IgG, by enhancing glycolysis and the lactate cycle, induces metabolic reprogramming and thereby promotes the development of TNBC, making it a promising target for targeted therapy in TNBC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"96"},"PeriodicalIF":7.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aromatase inhibitors therapy and major osteoporotic fracture risk in postmenopausal breast cancer patients: a nationwide real-world cohort study.","authors":"Pin-Han Liu, Ching-Fang Tsai, Yu-Chen Hsu, Cheng-Yi Wu, Hsin-Yi Yang","doi":"10.1186/s13058-025-02050-5","DOIUrl":"10.1186/s13058-025-02050-5","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"95"},"PeriodicalIF":7.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of vitronectin as a potential non-invasive biomarker of metastatic breast cancer using a label-free LC-MS/MS approach.","authors":"Roopali Roy, Elisa M Schunkert, Petra Olivova, Martin Gilar, Scott Geromanos, Guo-Zhong Li, John Gebler, Adelle Dagher, Andrew El-Hayek, Rama Aldakhlallah, Steven J Staffa, David Zurakowski, Margaret Lotz, Susan Pories, Marsha A Moses","doi":"10.1186/s13058-025-02053-2","DOIUrl":"10.1186/s13058-025-02053-2","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is a complex heterogenous disease that is a leading cause of death in women. For patients with early stage disease following primary BC therapy, approximately 30% will develop metastatic BC (MBC). The median survival of MBC patients is ~ 2-3 yr. While the early detection and monitoring of BC progression have improved prognosis and reduced BC-related mortality, there is a lack of long-term surveillance strategies for monitoring patients for recurrence of MBC. The aim of our study was to identify non-invasive urinary biomarkers for detection and monitoring of MBC.</p><p><strong>Methods: </strong>We have conducted a comparative label-free LC-MS/MS analysis of the urinary proteome of patients with MBC and healthy age-matched, sex-matched controls (HC). A hybrid quadrupole time of flight (Q-Tof™) mass spectrometer was used for urine analysis via liquid chromatography (LC) with tandem mass spectrometry (MS/MS). Retrospective analysis of urine samples from MBC and locally invasive breast cancer (IBC) patients as well as HC was conducted. Diagnostic accuracies of candidate markers were validated using independent training and validation sets according to the REMARK criteria.</p><p><strong>Results: </strong>Using this approach, we have identified 212 urinary proteins of which 83 and 25 were unique to the MBC and HC groups, respectively. Upregulated proteins in the MBC cohort were associated with angiogenesis, Ca²⁺ homeostasis, apoptosis, proteolysis, extracellular matrix regulation, cell adhesion and protein synthesis pathways. A specific non-invasive metastasis signature comprised of candidate biomarkers (urinary CALB1, S100A8, ZAG, VTN and TN) were validated and analyzed via monospecific ELISA assays. Urinary vitronectin (uVTN) levels correlated with disease status and were significantly higher in samples from MBC compared to those from IBC patients and HC. uVTN alone (cutoff > 500 ng/ml) could discriminate between HC and MBC groups (AUC = 0.782, P < 0.001). Longitudinal analysis of samples from MBC patients indicated a strong correlation between uVTN levels and disease status.</p><p><strong>Conclusions: </strong>Our findings suggest that uVTN is a promising and non-invasive biomarker for the diagnosis and monitoring of MBC. While future validation in larger cohorts should be done, these results identify a novel urinary protein that represents the first non-invasive diagnostic test for monitoring BC progression and recurrence.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"94"},"PeriodicalIF":7.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}