The Journal of Liquid Biopsy最新文献

{"title":"Liquid biopsy biomarkers in cervical cancer: A systematic review and meta-analysis","authors":"Isaac Kinyua Njangiru ,&nbsp;Bizhar Ahmed Tayeb ,&nbsp;Hazhmat Ali ,&nbsp;Rafl M. Kamil","doi":"10.1016/j.jlb.2025.100328","DOIUrl":"10.1016/j.jlb.2025.100328","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Liquid biopsy biomarkers are emerging as vital tools for cancer screening and diagnosis, offering a noninvasive and accurate approach to early malignancy detection. This study aimed to assess the diagnostic performance of circulating biomarkers in cervical cancer (CC).</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across the Cochrane Library, PubMed, SCOPUS, and Web of Science, identifying 130 studies, of which 11 met the inclusion criteria. Data on true and false positives and negatives were extracted to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratios (DORs), and 95 % confidence intervals (CIs). Study quality and risk of bias were evaluated using the QUADAS-2 tool, while publication bias was assessed via Deeks’ funnel plot.</div></div><div><h3>Results</h3><div>The meta-analysis included 1301 patients, 670 healthy controls, and 438 individuals with benign or precancerous lesions. Pooled sensitivity was 0.68 (95 % CI: 0.65–0.70), and specificity was 0.84 (95 % CI: 0.81–0.86). The DOR was 61.10 (95 % CI: 32.20–115.9), with an area under the curve (AUC) of 0.95. Most studies demonstrated a low risk of bias, and no significant publication bias was observed (P = 0.06). Plasma-based liquid biopsies and miRNA biomarkers exhibited superior diagnostic performance.</div></div><div><h3>Conclusions</h3><div>These findings suggest that liquid biopsy biomarkers may substantially enhance the accuracy of cervical cancer detection, representing a promising strategy for early diagnosis.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100328"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer in a drop: Liquid biopsy highlights from the American Society of Clinical Oncology (ASCO) 2025 annual congress","authors":"Canio Martinelli ,&nbsp;Roberto Borea ,&nbsp;Maheswaran Shivahamy ,&nbsp;Angelo Dipasquale ,&nbsp;Erick F. Saldanha ,&nbsp;Nadia Ghazali ,&nbsp;Eleonora Nicolo ,&nbsp;Pavel Stejskal ,&nbsp;Letizia Pontolillo ,&nbsp;Carolina Reduzzi","doi":"10.1016/j.jlb.2025.100320","DOIUrl":"10.1016/j.jlb.2025.100320","url":null,"abstract":"<div><div>Over the past decade, liquid biopsy has progressively expanded its role in oncology, supported by mounting evidence demonstrating an increasing number of clinical applications. At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, liquid biopsy emerged as a central theme across multiple sessions, with more than 700 abstracts, investigating the clinical utility of liquid biopsy across a wide range of tumor types and disease stages. Applications presented included cancer screening, minimal residual disease (MRD) detection, management of metastatic disease, and potential use for matching patients to clinical trials. This editorial, authored on the behalf of the Young Committee of the International Society of Liquid Biopsy (ISLB) highlights the result of selected studies, grouped by tumor type.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100320"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype independent capture of circulating tumor cell using magnetic platelet decoys","authors":"Kenise Morris ,&nbsp;Colette Li ,&nbsp;Sasmit Sarangi ,&nbsp;Anne-Laure Papa","doi":"10.1016/j.jlb.2025.100326","DOIUrl":"10.1016/j.jlb.2025.100326","url":null,"abstract":"<div><div>Circulating tumor cells (CTCs) are an essential biomarker for metastatic disease as they provide valuable information regarding the primary tumor, metastatic potential, potential prognosis, as well as aid in patient monitoring and guiding personalized therapy. Successful detection, isolation, and enumeration of CTCs remains a challenge due to their rarity in blood and biological heterogeneity. Though traditionally known for their roles in maintaining hemostasis and promoting wound healing, platelets significantly contribute to cancer metastasis by interacting with CTCs in the bloodstream. These interactions protect CTCs from shear stress and immune detection, facilitate their arrest in blood vessels, and ultimately promote metastatic spread to distant tissues. We describe a system that leverages platelet-cancer cell interactions to target and retrieve CTCs from a liquid biopsy sample by engineering magnetic platelet decoys. Conventional techniques typically rely on specific markers on the CTC surface (most commonly EpCAM). Our approach begins with engineering platelet decoys that lose their functional ability but retain some functional surface receptors that enable their ability to interact with other cells, followed by ION (iron oxide nanoparticle) loading which permits CTC capture <em>via</em> magnetic retrieval. Because our non-antibody-based approach relies on magnetic platelet decoy-CTC interactions, we infer that our system is applicable to CTCs of various origins and phenotypes. We have characterized and shown that our system can effectively interact with various cell lines (MDA-MB-231, MCF-7, A549) and capture these cells in spiked whole blood with a retrieval rate of at least 58.5%. This study has also demonstrated that the magnetic platelet decoys remain stable and effective after cryopreservation. While experiments used freshly prepared magnetic platelet decoys, stability assessment demonstrated that magnetic platelet decoys stored for one month at −20 °C with cryoprotectant retain their activity and ability to interact with other cells, supporting their practical use in future applications.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100326"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BLOODPAC's collaborations with European Union liquid biopsy initiatives","authors":"Jennifer Dickey ,&nbsp;Elaine Katrivanos ,&nbsp;Lauren C. Leiman ,&nbsp;Abde M. Abukhdeir ,&nbsp;Antonella Cardone ,&nbsp;Banu Saritas-Yildirim ,&nbsp;Carlos Galamba ,&nbsp;Cheyenne Jankiewicz ,&nbsp;Christian Rolfo ,&nbsp;Deepshikha Bhandari ,&nbsp;Emily Finnegan ,&nbsp;Francesca Fenizia ,&nbsp;Haydar Celik ,&nbsp;Ingrid Mehlhorn ,&nbsp;Jillian Walker ,&nbsp;Jose Luis Costa ,&nbsp;Kathy Williams ,&nbsp;Mark Sewart ,&nbsp;Matias Olsen ,&nbsp;Michael Wierzba ,&nbsp;Veronica Gonzales","doi":"10.1016/j.jlb.2025.100321","DOIUrl":"10.1016/j.jlb.2025.100321","url":null,"abstract":"<div><div>The adoption of liquid biopsy into clinical practice has revolutionized the landscape of cancer diagnostics and treatment monitoring. In the U.S., the Blood Profiling Atlas in Cancer (BLOODPAC) has significantly supported the advancement of these technologies through consensus building [<span><span>1</span></span>]. In collaboration with the United States (US) Food and Drug Administration (FDA), BLOODPAC has developed minimum technical data elements (MTDEs) and analytical validation protocols to streamline the assay development and regulatory assessment of liquid biopsy-based technologies. Additionally, BLOODPAC has established a pre-competitive data sharing model to support clinical implementation.</div><div>The European Union faces regulatory and access challenges that hinder widespread adoption of liquid biopsy technologies. Complexities under the In Vitro Diagnostic Regulation (IVDR) and Clinical Trials Regulation (CTR) have introduced variability and delays across member states. While recognizing Europe's strengths in developing robust frameworks and high standards for advancing precision oncology, this paper explores how BLOODPAC's efforts—particularly in standardization, validation, and data sharing—could inform and complement EU initiatives. BLOODPAC's experience in developing fit-for-purpose validation frameworks and fostering regulatory-industry dialogue offers particularly relevant insights for addressing EU-specific challenges. This paper proposes opportunities for collaboration and guidance development that could enhance European access to liquid biopsy-based tests for precision medicine, ultimately improving patient access and outcomes for cancer care and management.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100321"},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid biopsy- A pivotal test to help navigate clinical decisions at a precision center in India!","authors":"Sewanti Limaye ,&nbsp;Aditya Shreenivas ,&nbsp;Darshana Patil ,&nbsp;Janani Sambath ,&nbsp;Irene A. George ,&nbsp;Anjali Parab ,&nbsp;Aakriti Datta ,&nbsp;Punita Jain ,&nbsp;Shambhavi Singh ,&nbsp;Chetan Madre ,&nbsp;Pritam Kataria ,&nbsp;Darshit Shah ,&nbsp;Niyati Shah ,&nbsp;Ruturaj Deshpande ,&nbsp;Rajan Datar ,&nbsp;Prashant Kumar","doi":"10.1016/j.jlb.2025.100323","DOIUrl":"10.1016/j.jlb.2025.100323","url":null,"abstract":"<div><div>Liquid biopsy, specifically circulating tumor DNA (ctDNA) analysis, has emerged as a transformative tool in precision oncology, providing real-time, minimally invasive characterizations of the tumor and tumor dynamics. While tissue biopsy is a critical tool for baseline diagnosis of malignancy, it is often limited by sampling constraints and an inability to capture tumor heterogeneity. In this study, we explored the clinical utility of serial ctDNA testing in guiding therapeutic decisions across a cohort of 30 patients with diverse solid tumors. Our real-world analysis demonstrates that ctDNA profiling meaningfully influenced treatment escalation, de-escalation, disease monitoring, and early relapse prediction. Cases where ctDNA positivity indicated minimal residual disease prompted timely escalation of therapy, while ctDNA clearance allowed safe treatment de-intensification, minimizing toxicity without compromising outcomes. Longitudinal ctDNA monitoring provided a dynamic, non-invasive method for assessing treatment response and detecting recurrence months before radiological progression. Our study highlights the potential of integrating liquid biopsy into routine clinical practice to enable dynamic treatment monitoring, early detection of therapeutic resistance, and more informed, personalized decision-making across various cancer types.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100323"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic accuracy of next-generation sequencing in advanced NSCLC","authors":"Elaine Yee-Ling Ko ,&nbsp;Jason Wing Hon Wong ,&nbsp;David Jen Hao Shih ,&nbsp;Isaac Ho ,&nbsp;Ben Man Fei Cheung ,&nbsp;Matthew Kin-Liang Chiu ,&nbsp;Dennis Kwok-Chuen Leung ,&nbsp;Anne Wing-Mui Lee ,&nbsp;Victor Ho-Fun Lee ,&nbsp;Aya El Helali","doi":"10.1016/j.jlb.2025.100325","DOIUrl":"10.1016/j.jlb.2025.100325","url":null,"abstract":"<div><h3>Background</h3><div>Comprehensive genomic profiling is crucial for guiding treatment in advanced non-small cell lung cancer (NSCLC). However, tumor tissue-based targeted panel next-generation sequencing (TP-NGS) faces challenges, such as inadequate tissue sampling. Circulating tumor DNA (ctDNA) from peripheral blood has emerged as an alternative.</div></div><div><h3>Methods</h3><div>Participants with advanced NSCLC were enrolled in a Precision Oncology Program to enhance personalized treatments. TP-NGS was conducted using FoundationOne®CDx and FoundationOne®Liquid CDx. The study included an unpaired cohort and a paired cohort. We evaluated the impact of ctDNA tumor fraction (TF) on TP-NGS diagnostic accuracy, focusing on sensitivity as a key metric of efficacy.</div></div><div><h3>Results</h3><div>We prospectively analyzed data from 561 patients, of whom 62·4 % (n = 340) were in the unpaired cohort and 39·4 % (n = 221) were in the paired cohort. Specifically, in the paired cohort, actionable mutations were found in 50·2 % (n = 111) of patients, predominantly common <em>EGFR</em> mutations in 65·8 % (n = 73). The ctDNA TF high (TF&gt;1 %, range 1 %–72 %) group had a 100 % positive percent agreement (PPA), while the ctDNA TF low group had a PPA of 47·5 % for actionable mutations. The correlation between bTMB and tTMB was 0·13 for ctDNA TF low versus 0·71 for ctDNA TF high. The PPA for bTMB was 31·3 % for ctDNA TF low and 92·3 % for ctDNA TF high, with negative percent agreement (NPA) at 100 % and 85·6 %, respectively.</div></div><div><h3>Conclusion</h3><div>In the context of high ctDNA TF, blood-based TP-NGS can detect clinically actionable mutations and may effectively replace tissue biopsies when obtaining tumor tissue is impractical.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100325"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation leukemia diagnostics: Integrating LC-MS/MS proteomics with liquid biopsy platforms","authors":"Vivek Singh","doi":"10.1016/j.jlb.2025.100324","DOIUrl":"10.1016/j.jlb.2025.100324","url":null,"abstract":"<div><div>Diagnosing leukemia often depends on invasive bone marrow biopsies, which can be painful and may fail to detect the early stages of the disease. Liquid biopsy, a minimally invasive method that analyzes circulating biomarkers in blood, has emerged as a powerful tool for the early detection of leukemia. Among emerging technologies, liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables high-throughput and sensitive profiling of blood-based proteins, thereby creating new opportunities for biomarker discovery. This mini-review highlights the clinical potential of LC-MS/MS in liquid biopsy for leukemia, with a focus on T-cell acute lymphoblastic leukemia (T-ALL). Recent proteomic studies have identified distinct protein signatures in the blood of T-ALL patients, such as XRRA1, CPNE4, and S100A8, which show substantial diagnostic value. We also address similar applications in acute myeloid leukemia (AML), the challenges of clinical translation, and the future integration of proteomics with multi-omics diagnostic platforms. Importantly, we discuss the limitations of current studies (e.g., small cohorts, limited diversity, and reproducibility issues) and the path toward clinical implementation, including validation in larger trials, regulatory considerations, cost-effectiveness, and the need for standardized protocols. LC-MS/MS-driven liquid biopsy represents a promising advancement toward earlier, less invasive, and more precise leukemia diagnostics, provided that robust validation and harmonization efforts are successful.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100324"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a liquid biopsy assay with increased sensitivity for clinical comprehensive genomic profiling","authors":"Xavier S. Bower ,&nbsp;Jan Wignall ,&nbsp;Matthew G. Varga ,&nbsp;Joyce Zhu ,&nbsp;Michael O'Sullivan ,&nbsp;Naomi E. Searle ,&nbsp;Lenny K. Hong ,&nbsp;Turgut Dogruluk ,&nbsp;Zeqian Li ,&nbsp;Tiffany E. Farmer ,&nbsp;Emilio Rosas-Linhard ,&nbsp;Jason Luong ,&nbsp;Esther Lin ,&nbsp;Marie Erica Simon ,&nbsp;David S. Tsao ,&nbsp;John R. ten Bosch ,&nbsp;Gary Palmer ,&nbsp;Ajeet Gajra ,&nbsp;Chanh Huynh ,&nbsp;Wen Zhou","doi":"10.1016/j.jlb.2025.100322","DOIUrl":"10.1016/j.jlb.2025.100322","url":null,"abstract":"<div><div>Recent advancements in precision oncology have affirmed the need for comprehensive genomic profiling (CGP) liquid biopsy assays with increased sensitivity, especially for detecting alterations in tumors which shed circulating tumor DNA (ctDNA) at low abundance. Such tests could address the limitations of tissue biopsies while simultaneously enhancing the detection of clinically actionable variants. This study included analytical and clinical validation studies of Northstar Select, a plasma-based, tumor-naive CGP assay covering 84 genes. The assay detects SNV/Indels, CNVs (gain and loss), fusions, and microsatellite instability (MSI-H). A retrospective analysis of 674 analytical patient samples collected during routine care in the United States, covering various solid tumor types, was conducted to investigate performance across tumor types. In addition, clinical validation was conducted in a prospective head-to-head comparison study of 182 patients, assessing the performance of Northstar Select and on-market CGP liquid biopsy assays. Analytical validation demonstrated a 95 % Limit of Detection of 0.15 % variant allele frequency (VAF) for SNV/Indels, which was confirmed by digital droplet PCR. Northstar Select demonstrated sensitive detection of CNVs in liquid down to 2.11 copies for amplifications and 1.80 copies for losses, and 0.30 % for gene fusions, addressing a key challenge in liquid biopsy testing. It outperformed on-market CGP assays, identifying 51 % more pathogenic SNV/indels and 109 % more CNVs. Additionally, this resulted in 45 % fewer null reports with no pathogenic or actionable results. The majority (91 %) of additional clinically actionable SNV/indels found were detected below 0.5 % VAF. Northstar Select demonstrated analytical and clinical validity, with high sensitivity across all variant classes. The low LOD allows for reliable detection of variants at lower VAFs compared to existing commercial assays. Northstar Select can therefore enhance clinical decision-making by providing the opportunity to identify more actionable genomic alterations, which may be especially beneficial for patients with low-shedding tumors.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100322"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonization trial on ESR1 testing strategies in ER+/HER2- breast cancer patients: an Italian experience","authors":"Francesco Pepe ,&nbsp;Gianluca Russo ,&nbsp;Konstantinos Venetis ,&nbsp;Claudia Scimone ,&nbsp;Lucia Palumbo ,&nbsp;Mariantonia Nacchio ,&nbsp;Domenica di Giovanni ,&nbsp;Claudia Sarracino ,&nbsp;Ilaria Tomaiuolo ,&nbsp;Elisabetta Zulato ,&nbsp;Matteo Fassan ,&nbsp;Daniela Righi ,&nbsp;Giuseppe Perrone ,&nbsp;Dario de Biase ,&nbsp;Gabriele Casati ,&nbsp;Fabio Pagni ,&nbsp;Lucia Gullotti ,&nbsp;Antonio Rizzo ,&nbsp;Alessandro Perez ,&nbsp;Antonio Russo ,&nbsp;Umberto Malapelle","doi":"10.1016/j.jlb.2025.100314","DOIUrl":"10.1016/j.jlb.2025.100314","url":null,"abstract":"<div><h3>Aims</h3><div>To date, <em>ESR1</em> activating mutations acts as key player to clinically stratify estrogen receptor (ER)+/HER2-advanced breast cancer (BC) patients eligible to novel new generation oral Selective Estrogen Receptor Degraders (SERD) relapsing after first line aromatase inhibitors. Liquid biopsy represents the most useful biological source to detect <em>ESR1</em> activating mutations in clinical setting, but the lack of standardized pre-analytical and analytical procedures drastically impacts on detection rate of <em>ESR1</em> mutations in diagnostic specimens. Here, we sought to harmonize technical procedures comparing technical performance of diagnostically available testing strategies on a series of three reference specimens (sample A, B, C) harboring <em>ESR1</em> p.D538G mutation at different mutant allele fraction (MAF) (5.0 %, 1.0 %, 0.5 %) shared with n = 10 Italian referral institutions.</div></div><div><h3>Methods</h3><div>A total of 10 μl of gDNA from each reference sample built to mimic clinically detectable <em>ESR1</em> molecular alteration (5.0 %, 1.0 %, 0.5 % VAF) was shipped by coordinator institution to each participating group to test p.D538G <em>ESR1</em> alteration leveraging own routinely available testing strategy. Artificial reference sample was previously validated by the University of Naples Federico II before arranging the shipment.</div></div><div><h3>Results</h3><div><em>ESR1</em> exon 10 p.(D538G) hotspot mutation was successfully identified in 90.0 % of samples A, B whereas 8 out of 10 (80.0 %) participating institutions detected sample referenced alteration in sample C. No statistically significant variations were observed between dPCR and NGS based workflows in terms of detectability rate on standard reference samples. A single participating institution (ID#5) failed to detect p.(D538G) <em>ESR1</em> alteration but supervised procedures by coordinator institution enabled to detect referenced mutation in engineered reference samples set adopting an orthogonal technology (dPCR). In addition, NGS and dPCR platforms displayed a similar technical performance in detecting <em>ESR1</em> across samples A-C.</div></div><div><h3>Conclusions</h3><div>NGS and dPCR systems may be considered valid technical solutions to target low frequency <em>ESR1</em> alterations in diagnostic routine samples. Harmonized ring trials are key weapons to standardize analytical and post-analytical procedures optimizing clinical stratification of BC patients</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100314"},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multivariate cell-based liquid biopsy for lung nodule risk stratification: Analytical validation and early clinical evaluation","authors":"Jason D. Berndt ,&nbsp;Fergal J. Duffy ,&nbsp;Mark D. D'Ascenzo ,&nbsp;Leslie R. Miller ,&nbsp;Yijun Qi ,&nbsp;G. Adam Whitney ,&nbsp;Samuel A. Danziger ,&nbsp;Anil Vachani ,&nbsp;Pierre P. Massion ,&nbsp;Stephen A. Deppen ,&nbsp;Robert J. Lipshutz ,&nbsp;John D. Aitchison ,&nbsp;Jennifer J. Smith","doi":"10.1016/j.jlb.2025.100313","DOIUrl":"10.1016/j.jlb.2025.100313","url":null,"abstract":"<div><h3>Background</h3><div>The Indicator Cell Assay Platform (iCAP) is a novel tool for blood-based diagnostics that uses living cells as biosensors to integrate and amplify weak, multivalent disease signals present in patient serum. In the platform, standardized cells are exposed to small volumes of patient serum, and the resulting transcriptomic response is analyzed using machine learning tools to develop disease classifiers.</div></div><div><h3>Methods</h3><div>We developed a lung cancer-specific iCAP (LC-iCAP) as a rule-out test for the management of indeterminate pulmonary nodules detected by low-dose CT screening. This included assay parameterization, analytical reproducibility testing, and selection of a fixed 85-gene feature set for future clinical validation and regulatory development. Clinical performance was estimated using a prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) study design comprising 176 samples. Classifier variants were trained by nested cross validation using subsets of the 85 genes, and selected variants were evaluated by temporal blind validation using 39 control and 40 case samples (72 % Stage I, 22 % Stage II cancer).</div></div><div><h3>Results</h3><div>The assay showed excellent reproducibility across various conditions and cell lineages, and case versus control transcriptomic signals were enriched for hypoxia-responsive genes, consistent with known lung cancer biology. Two models demonstrated discriminative ability in blind validation, one with AUC = 0.64 (95 % CI: 0.51–0.76). Post hoc integration with CT imaging features yielded a combined model with 90 % sensitivity, 64 % specificity, and 95 % negative predictive value at 25 % prevalence, suggesting clinical utility and surpassing performance of existing rule-out tests.</div></div><div><h3>Conclusion</h3><div>This study establishes the analytical reproducibility and biological relevance of the LC-iCAP. While clinical validation is preliminary, the results support the assay's potential utility in lung nodule management. The study introduces a new paradigm of using scalable and cost-effective cell-based biosensor assays for liquid biopsies. With a multivariate readout, the platform is amenable to precision medicine applications such as multi-cancer early detection.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100313"},"PeriodicalIF":0.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}