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liquid biopsy technologies: innovations and future directions in breast cancer biomarker detection

BIOMEDICAL MICRODEVICES 2025年第1期27卷 1-21页

作者： Cao, Linhong Duan, Qingli Zhu, Zixin Xu, Xuejing Liu, Jinbo Li, Baolin Southwest Med Univ Affiliated Hosp Dept Lab Med 25 Taiping St Luzhou 646000 Sichuan Peoples R China Sichuan Prov Engn Technol Res Ctr Mol Diag Clin Di Luzhou Peoples R China Mol Diag Clin Dis Key Lab Luzhou Sichuan Peoples R China

Globally, breast cancer is the most frequent type of cancer, and its early diagnosis and screening can significantly improve the probability of survival and quality of life of those affected. liquid biopsy-based targets such as circulating tumor cells, circulating tumor DNA, and exosomes have been instrumental in the early discovery of cancer, and have been found to be effective in stage therapy, recurrence monitoring, and drug selection. Biosensors based on these target related biomarkers convert the tested substances into quantifiable signals such as electrical and optical signals through signal transduction, which has the advantages of high sensitivity, simple operation, and low invasiveness. This review provides an overview of the latest progress of liquid biopsy biomarkers in the diagnosis, prognosis and treatment of breast cancer, compares the application and advantages of different biosensors based on these biomarkers in the diagnosis of breast cancer, and analyzes the limitations and solutions of biosensor based methods.

关键词： liquid biopsy Biosensor Breast cancer Biomarker

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liquid biopsy for breast cancer and other solid tumors: a review of recent advances

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BREAST CANCER 2025年第1期32卷 33-42页

作者： Ohmura, Hirofumi Hanamura, Fumiyasu Okumura, Yuta Ando, Yuki Masuda, Takaaki Mimori, Koshi Akashi, Koichi Baba, Eishi Kyushu Univ Grad Sch Med Sci Dept Oncol & Social Med 3-1-1 MaidashiHigashi Ku Fukuoka 8128582 Japan Kyushu Univ Beppu Hosp Dept Internal Med Oita Japan Natl Hosp Org Kyushu Canc Ctr Dept Gastrointestinal & Med Oncol Fukuoka Japan Kyushu Univ Beppu Hosp Dept Surg Oita Japan Kyushu Univ Grad Sch Med Sci Dept Med & Biosyst Sci Fukuoka Japan

liquid biopsy using circulating tumor DNA (ctDNA) has been reported to be less invasive and effective for comprehensive genetic analysis of heterogeneous solid tumors, including decision-making for therapeutic strategies, predicting recurrence, and detecting genetic factors related to treatment resistance in various types of cancers. Breast cancer, colorectal cancer, and lung cancer are among the most prevalent malignancies worldwide, and clinical studies of liquid biopsy for these cancers are ongoing. liquid biopsy has been used as a companion diagnostic tool in clinical settings, and research findings have accumulated, especially in cases of colorectal cancer after curative resection and non-small cell lung cancer (NSCLC) after curative chemoradiotherapy, in which ctDNA detection helps predict eligibility for adjuvant chemotherapy. liquid biopsy using ctDNA shows promise across a wide range of cancer types, including breast cancer, and its clinical applications are expected to expand further through ongoing research. In this article, studies on liquid biopsy in breast cancer, colorectal cancer, and NSCLC are compared focusing on ctDNA.

关键词： liquid biopsy ctDNA Colorectal cancer Lung cancer Breast cancer

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liquid biopsy using non-coding RNAs and extracellular vesicles for breast cancer management

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BREAST CANCER 2025年第1期32卷 16-25页

作者： Hashimoto, Kazuki Ochiya, Takahiro Shimomura, Akihiko Natl Ctr Global Hlth & Med Dept Breast Surg Oncol 1-21-1 Toyama Shinjuku Ku Tokyo 1628655 Japan Tokyo Med Univ Inst Med Sci Dept Mol & Cellular Med 6-7-1 Nishishinjuku Shinjuku Ku Tokyo 1600023 Japan Natl Ctr Global Hlth & Med Dept Breast & Med Oncol 1-21-1 Toyama Shinjuku Ku Tokyo 1628655 Japan

This article examines liquid biopsy using non-coding RNAs and extracellular vesicles in detail. liquid biopsy is emerging as a prominent non-invasive diagnostic tool in the treatment of breast cancer. We will elucidate the roles of these molecules in early detection, monitoring treatment effectiveness, and prognostic assessment of breast cancer. Additionally, the clinical significance of these molecules will be discussed. We aim to delve into the distinct characteristics of these molecules and their possible roles in breast cancer management, with an anticipation of their contribution to future diagnostic and therapeutic advancements.

关键词： Breast cancer liquid biopsy miRNA Non-coding RNA Extracellular vesicles

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liquid biopsy in Neuropsychiatric Disorders: A Step Closer to Precision Medicine

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MOLECULAR NEUROBIOLOGY 2025年第3期62卷 3462-3479页

作者： El-Ahmad, Perla Mendes-Silva, Ana Paula Diniz, Breno S. Univ Connecticut Hlth Ctr UConn Ctr Aging 263 Farmington Ave Farmington CT 06030 USA Campbell Family Mental Hlth Res Inst Ctr Addict & Mental Hlth CAMH Toronto ON Canada Univ Saskatchewan Dept Psychiat Saskatoon SK Canada

Psychiatric disorders are among the leading causes of disease burden worldwide. Despite their significant impact, their diagnosis remains challenging due to symptom heterogeneity, psychiatric comorbidity, and the lack of objective diagnostic tests and well-defined biomarkers. Leveraging genomic, epigenomic, and fragmentomic technologies, circulating cell-free DNA (ccfDNA)-based liquid biopsies have emerged as a potential non-invasive diagnosis and disease-monitoring tool. ccfDNA is a DNA species released into circulation from all types of cells through passive and active mechanisms and can serve as a biomarker for various diseases, namely, cancer. Despite their potential, the application of ccfDNA in neuropsychiatry remains underdeveloped. In this review, we provide an overview of liquid biopsies and their components, with a particular focus on ccfDNA. With a summary of pre-analytical practices and current ccfDNA technologies, we highlight the current state of research regarding the use of ccfDNA as a biomarker for neuropsychiatric disorders. Finally, we discuss future steps to unlock ccfDNA's potential in clinical practice.

关键词： liquid biopsy Cell-free Nucleic Acids Cell-free DNA Cell-free Mitochondrial DNA

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liquid biopsy-derived extracellular vesicle protein biomarkers for diagnosis and prognostic assessment of lung squamous cell carcinoma

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CANCER CELL INTERNATIONAL 2025年第1期25卷 1-18页

作者： Ma, Sheng Zhao, Na Dong, Xin Wang, Yaru Song, Lei Zheng, Ruiqi Zhi, Xiaochen Ma, Congcong Cheng, Shujun Li, Jie Liu, Yutao Xiao, Ting Chinese Acad Med Sci & Peking Union Med Coll Dept Etiol & Carcinogenesis State Key Lab Mol Oncol Natl Canc CtrNatl Clin Res Ctr CancCanc Hosp Beijing Peoples R China Dept Prote Tianjin Key Lab Clin Multiom Tianjin Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Natl Canc Ctr Dept Clin Lab Natl Clin Res Ctr CancCanc Hosp Beijing Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Natl Clin Res Ctr Canc Canc Hosp Dept Med OncolNatl Canc Ctr Beijing Peoples R China

BackgroundFor patients with nodules detected in imaging that are indeterminate for malignancy, achieving accurate, early, and non-invasive diagnosis of Lung Squamous Cell Carcinoma (LUSC) remains a significant challenge. Therefore, we aimed to establish diagnostic and prognostic models by identifying plasma extracellular vesicles (EVs) associated protein biomarkers specific to *** study employed a novel nanomaterial, NaY, for the enrichment of EVs from plasma. Validation was conducted through transmission electron microscopy, nanoparticle tracking analyses, and Western blotting. Machine learning algorithms were utilized to compute protein biomarkers associated with LUSC and establish a diagnostic model. Additionally, a prognostic prediction model for LUSC was developed using a combination of 101 machine learning algorithms. Risk scoring of patients was performed to explore the underlying reasons for prognostic differences between high and low-risk *** results of three experiments demonstrate that the new nanomaterial NaY effectively enriches EVs from plasma. Analysis of the enriched profile reveals pathways related to glycolysis/gluconeogenesis and carbon metabolism enriched in plasma EVs of LUSC patients. Thirty-eight LSCC-related EV biomarkers were identified, from which five proteins (TUBB3, RPS7, RPLP1, KRT2, and VTN) were selected to establish a diagnostic model distinguishing between benign and LUSC nodules. The diagnostic efficacy of RPS7 and VTN was further validated in independent samples using ELISA experiments. Furthermore, DPYD, GALK1, CDC23, UBE2L3, RHEB, and PSME1 were determined as potential prognostic biomarkers. Subsequently, risk scores were computed for each sample, classifying all patients into high and low-risk groups. Enrichment analysis revealed that EVs from the high-risk group contained proteins promoting cell proliferation and invasion, while those from the low-risk group were enriched in immune-related protein bi

关键词： liquid biopsy Machine learning EVs Protein biomarkers Diagnosis and prognosis of LUSC

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liquid biopsy for Spinal Tumors: On the Frontiers of Clinical Application

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GLOBAL SPINE JOURNAL 2025年第1_SUPPL期15卷 16S-28S页

作者： Tan, Sze Kiat Bettegowda, Chetan Yip, Stephen Sahgal, Arjun Rhines, Laurence Reynolds, Jeremy Lazary, Aron Laufer, Ilya Gasbarrini, Alessandro Dea, Nicolas Verlaan, J. J. Gokaslan, Ziya L. Fisher, Charles G. Boriani, Stefano Cecchinato, Riccardo Goodwin, Matthew L. Goodwin, C. Rory Charest-Morin, Raphaele Johns Hopkins Univ Sch Med Dept Neurosurg Baltimore MD USA Univ British Columbia Fac Med Dept Pathol & Lab Med Vancouver BC Canada Sunnybrook Odette Canc Ctr Dept Radiat Oncol Toronto ON Canada Univ Toronto Dept Radiat Oncol Toronto ON Canada Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX USA Univ Oxford Oxford Spinal Unit Oxford England Semmelweis Univ Dept Spine Surg Budapest Hungary Semmelweis Univ Dept Orthopaed Surg Budapest Hungary NYU Dept Neurosurg Grossman Sch Med New York NY USA Univ Bologna Rizzoli Inst Dept Orthoped Surg Bologna Italy Univ British Columbia Dept Orthoped Combined Neurosurg & Orthoped Spine Program 818 West 10th Ave Vancouver BC V5Z 1M9 Canada Univ Utrecht Univ Med Ctr Utrecht Dept Orthoped Surg Utrecht Netherlands Brown Univ Warren Alpert Med Sch Dept Neurosurg Providence RI USA IRCCS Galeazzi St Ambrogio Hosp GSpine4 Milan Italy Washington Univ St Louis Dept Orthoped Surg St Louis MO USA Duke Univ Med Ctr Dept Neurosurg Spine Div Durham NC USA

Study DesignNarrative *** article aims to provide a narrative review of the current state of research for liquid biopsy in spinal tumors and to discuss the potential application of liquid biopsy in the clinical management of patients with spinal *** comprehensive review of the literature was performed using PubMed, Google Scholar, Medline, Embase and Cochrane databases, and the review was limited to articles of English language. All the relevant articles which were identified to be related to liquid biomarker study in spinal tumors, were studied in full *** biopsy has revolutionized the field of precision medicine by guiding personalized clinical management of cancer patients based on the liquid biomarker status. In recent years, more research has been done to investigate its potential utilization in patients with tumors from the spine. Herein, we review the liquid biomarkers that have been proposed in different spine malignancies including chordoma, chondrosarcoma, Ewing sarcoma, osteosarcoma, astrocytoma and ependymoma. We also discuss the wide window of opportunity to utilize these liquid biomarkers in diagnosis, treatment response, monitoring, and detection of minimal residual disease in patients with spinal *** biomarkers, especially blood-derived circulating tumor DNA, has a promising clinical utility as they are disease-specific, minimally invasive, and the procedure is repeatable. Prospective studies with larger populations are needed to fully establish its use in the setting of spinal tumors.

关键词： liquid biopsy spinal tumors circulating tumor DNA blood biomarkers cerebrospinal fluid biomarker chordoma chondrosarcoma Ewing sarcoma osteosarcoma ependymoma

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liquid biopsy in organ damage: introduction of an innovative tool for assessing the complexity of blunt splenic injury

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EUROPEAN JOURNAL OF MEDICAL RESEARCH 2025年第1期30卷 1-5页

作者： Woehler, Aliona Wang, Bingduo Schwab, Robert Lukacs-Kornek, Veronika Willms, Arnulf G. Kornek, Miroslaw T. German Armed Forces Cent Hosp Dept Gen Visceral & Thorac Surg Koblenz Germany Rheinische Friedrich Wilhelms Univ Univ Hosp Dept Internal Med 1 Venusberg Campus 1 D-53127 Bonn Germany Rheinische Friedrich Wilhelms Univ Univ Hosp Inst Mol Med & Expt Immunol Bonn Germany

liquid biomarkers are essential in trauma cases and critical care and offer valuable insights into the extent of injury, prognostic predictions, and treatment guidance. They can help assess the severity of organ damage (OD), assist in treatment decisions and forecast patient outcomes. Notably, small extracellular vesicles, particularly those involved in splenic trauma, have been overlooked. Here, we reanalyzed our data and explored whether monocyte-derived small EVs are correlated with AAST score (American Association for the Surgery of Trauma) scoring and are sensitive enough to distinguish the severity of splenic trauma in our explorative study. There was a correlation between monocyte-derived small extracellular vesicles (EVs) and the AAST score (r(Sp) = 0.82, p < 0.001). Specifically, we observed that blood-borne small EVs originating from monocytes (CD9(+)CD14(+) sEVs) were directly correlated with AAST scores. These EVs were found to be significantly elevated in patients with complex spleen injuries (AAST I-IV with hemodynamic instability and need for operative management) in an incremental manner;these patients were typically classified as AAST grade II or higher, which frequently included accompanying solid organ injuries. Our initial discovery shows great promise and warrants further exploration. This could pave a novel future path for a new critical care management approach for splenic injuries. There may also be synergistic effects when combined with extended focused assessment with sonography in trauma (E-FAST) sonography, particularly in triage scenarios, where resource constraints prevent immediate access to a CT scan.

关键词： Biomarker Extracellular vesicles Exosomes NOM Spleen laceration liquid biopsy AAST Blunt splenic injury Trauma

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liquid biopsy in cancer management: Integrating diagnostics and clinical applications

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PRACTICAL LABORATORY MEDICINE 2025年 43卷 e00446页

作者： Pandey, Shashwat Yadav, Preeti Babasaheb Bhimrao Ambedkar Univ Sch Pharmaceut Sci Dept Pharmaceut Sci Vidya ViharRaebareli Rd Lucknow 226025 India

liquid biopsy is an innovative, minimally invasive diagnostic tool revolutionizing cancer management by enabling the detection and analysis of cancer-related biomarkers from bodily fluids such as blood, urine, or cerebrospinal fluid. Unlike traditional tissue biopsies, which require invasive procedures, liquid biopsy offers a more accessible and repeatable method for tracking cancer progression, detecting early-stage cancers, and monitoring therapeutic responses. The technology primarily focuses on analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and other cancer-derived genetic materials. These biomarkers provide critical information on tumor heterogeneity, mutation profiles, and potential drug resistance. In clinical practice, liquid biopsy has demonstrated its utility in identifying actionable mutations, guiding personalized treatment strategies, and assessing minimal residual disease (MRD). While liquid biopsy holds immense promise, challenges related to its sensitivity, specificity, and standardization remain. Efforts to optimize pre-analytical and analytical processes, along with the establishment of robust regulatory frameworks, are crucial for its widespread clinical adoption. This abstract highlights the transformative potential of liquid biopsy in cancer diagnosis, prognosis, and treatment monitoring, emphasizing its role in advancing personalized oncology. Further research, clinical trials, and regulatory harmonization will be vital in realizing its full potential in precision cancer care.

关键词： liquid biopsy Cancer Tissue biopsy Personalized medicine

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Interfacial cfDNA Enrichment and Amplification with On-Chip Thermoplasmonics for Highly Sensitive Cancerous liquid biopsy

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ADVANCED SCIENCE 2025年第4期12卷 e2409708页

作者： Wang, Danhua Liu, Linlin Chi, Wenjing Liu, Zhenping Wu, Jiayun Liang, Yirou He, Fei Zhang, Ruixiang Huang, Pengxin Li, Yunbo Qiu, Guangyu Shanghai Jiao Tong Univ Inst Med Robot Sch Biomed Engn Shanghai 200240 Peoples R China Fudan Univ Huadong Hosp Dept Lab Med Shanghai 200031 Peoples R China First Peoples Hosp Linping Dist Hangzhou 311100 Zhejiang Peoples R China

Tumor-derived cell-free DNA (cfDNA) has been exploited as an effective liquid biopsy biomarker for early cancer diagnosis. However, the fragmented and low-abundance nature in circulating blood pose challenges for highly sensitive cfDNA quantification. Herein, a multifunctional plasmonic biosensor termed Interfacial cfDNA Enrichment, Amplification and Sensing with on-chip Thermoplasmonics (INEAST) is developed for cfDNA-based liquid biopsy and lung cancer diagnosis. The INEAST biosensor achieved in situ thermoregulation and label-free cfDNA biosensing by simultaneously harnessing interfacial thermoplasmonics and localized surface plasmon resonance. Typical cfDNA biomarkers, including epidermal growth factor receptor (EGFR), tumor protein 53 (TP53), phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and cyclin-dependent kinase inhibitor (CDKN2A), are quantified with detection limits down to femtomolar-level. Through further validation using blood samples from lung cancer patients, the proposed INEAST bioassays demonstrated superior reliability for lung cancer screening, particularly when combined with clinically available tumor-protein metrics. This study demonstrated that the INEAST biosensor enables rapid and sensitive cfDNA quantification, yielding a promising and compatible liquid biopsy for early-stage lung cancer diagnosis.

关键词： biosensors cell-free DNA liquid biopsy lung cancer nucleic acid amplification thermoplasmonics

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Immunofluorescent analysis of exosomes using a microchip filled with transparent antibody-conjugated beads for breast cancer liquid biopsy

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ANALYTICA CHIMICA ACTA 2025年 1345卷 343743页

作者： Li, Na Cheng, Cheng Wu, Di Song, Zixuan Wang, Bei Li, Guiying Yang, Fang Jilin Univ Sch Life Sci Key Lab Mol Enzymol & Engn Minist Educ 2699 Qianjin St Changchun 130012 Peoples R China

Background: Exosomes represent optimal biomarkers for liquid biopsy. Current exosome-based methods are still limited by isolation methods, long processing times, complex structure, low accuracy, large sample volume consumption, and the influence of chemical reagents on the analysis results. Result: To overcome these challenges, a novel microfluidic approach that employs continuous, rapid, and efficient processes is proposed for the capture and enriching exosomes using the optical transparent antibody-conjugated microbeads within the chip. By interfering with laminar flow, increasing mass transfer efficiency, expanding the specific reaction area, and concentrating the fluorescent signal, the microbeads raise the sensitivity of the detection. Furthermore, multiple biomarkers of a single disease could be detected simultaneously by multi-color labeling with a single sample injection. This method required only 50 mu L of plasma sample for detection within 35 min, demonstrating a low detection limit of 2.61 x 103 exosomes/mu L, coupled with high reproducibility, stability, and specificity. We evaluated the diagnostic potential for breast cancer (BC) by analyzing plasma exosomes in samples from 15 patients with BC and 15 healthy individuals. The identification of total exosomes, EpCAM-positive exosomes, and MUC1-positive exosomes demonstrated a strong ability to distinguish between cancer patients and healthy individuals, as indicated by area under curve (AUC) values of 0.88, 0.98, and 0.99, respectively. The integrated multi-biomarker detection strategy achieved the highest of diagnostic accuracy and specificity (SUM, AUC = 1.0). Significance: This study presents a novel exosome-based liquid biopsy strategy, which is expected to enhance the accuracy and efficiency of early diagnosis for cancer and other diseases.

关键词： liquid biopsy Microfluidic chip Breast cancer Exosomes Immunofluorescent assay

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