The Journal of Liquid Biopsy最新文献

{"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":"2025-12-01","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":"Circulating tumour DNA (ctDNA) as a predictor of progression-free and overall survival in non-resectable pancreatic cancer: a systematic review and meta-analysis","authors":"Mette M. Steiniche ,&nbsp;Louise B. Callesen ,&nbsp;Elizabeth H. Vlk ,&nbsp;Lise Ventzel ,&nbsp;Signe Timm ,&nbsp;Rikke F. Andersen ,&nbsp;Sidsel C. Lindgaard ,&nbsp;Torben F. Hansen ,&nbsp;Morten Ladekarl ,&nbsp;Karen-Lise G. Spindler","doi":"10.1016/j.jlb.2025.100441","DOIUrl":"10.1016/j.jlb.2025.100441","url":null,"abstract":"<div><h3>Background</h3><div>This systematic review and meta-analysis synthesised current evidence on circulating tumour DNA (ctDNA) for predicting clinical outcomes in patients with non-resectable pancreatic ductal adenocarcinoma (PDAC).</div></div><div><h3>Methods</h3><div>PubMed, Embase, and Cochrane databases were searched up to 31/01/2025. Eligible studies reported prognostic value of ctDNA in patients with non-resectable PDAC. Meta-analyses evaluated associations between baseline ctDNA and changes in ctDNA during treatment (ctDNA kinetics) and survival outcomes. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.</div></div><div><h3>Results</h3><div>Sixty-four studies involving 5652 patients with non-resectable PDAC were included, with 24 studies contributing to meta-analyses. High baseline ctDNA level implied shorter overall survival (OS; HR = 2.3, 95 % CI 1.9–2.8; n = 1883) and progression-free survival (PFS; HR = 2.1, 95 % CI 1.8–2.4; n = 1196). Unfavourable ctDNA kinetics were associated with shorter OS (HR = 3.1, 95 % CI 2.3–4.3; n = 269) and PFS (HR = 4.3, 95 % CI 2.6–7.2; n = 244). Thirty-three studies had high risk of bias in at least one QUIPS domain.</div></div><div><h3>Conclusion</h3><div>Baseline ctDNA and ctDNA kinetics demonstrate strong prognostic value in non-resectable PDAC. However, clinical translation is limited by methodological heterogeneity, notably the use of study-specific, non-validated thresholds. Standardised, externally validated thresholds for interpreting ctDNA changes are needed to support clinical implementation.</div></div><div><h3>Prospero</h3><div>CRD42023438774.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100441"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466249","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":"An innovative nuclear antigen-based approach for single-cell isolation of circulating tumor cells in adrenal cortical carcinoma","authors":"Giulia Cantini ,&nbsp;Francesca Salvianti ,&nbsp;Roberta Armignacco ,&nbsp;Arianna Pia Propato ,&nbsp;Letizia Canu ,&nbsp;Tonino Ercolino ,&nbsp;Anna Aurora Dedonno ,&nbsp;Chiara Lepri ,&nbsp;Massimo Mannelli ,&nbsp;Gabriella Nesi ,&nbsp;Serena Pillozzi ,&nbsp;Giuseppe Defazio ,&nbsp;Pamela Pinzani ,&nbsp;Michaela Luconi","doi":"10.1016/j.jlb.2025.100447","DOIUrl":"10.1016/j.jlb.2025.100447","url":null,"abstract":"<div><div>Adrenal cortical carcinoma (ACC) is a rare and aggressive endocrine tumor that originates from the adrenal cortex. Radical tumor resection remains the most effective therapy since survival dramatically drops when metastases are present at diagnosis. Hence, there is an urgent need for reliable biomarkers to enable early diagnosis, monitor minimal residual disease (MRD), and assess chemotherapy response. Circulating tumor cells (CTCs) detected via blood liquid biopsy may represent a valuable oncological marker in ACC patients. However, CTC isolation methods so far applied to ACC patients lack specificity, reproducibility and standardization, thus preventing the potential application of CTCs in the management of these patients.</div><div>In this study, we present a novel method for the specific and reproducible detection and analysis of single CTCs in ACC patients. This approach combines size- and mechanical property-based enrichment via the Parsortix® system with immunofluorescent detection and isolation of single CTCs using DEPArray® technology, targeting the steroidogenic factor-1 (SF1) nuclear adrenal cortex marker. Isolated CTCs undergo low-pass copy number alteration (CNA) analysis. This is the first report of a nuclear antigen-based method for isolating single CTCs in suspension, overcoming the limitations of membrane and cytokeratin markers commonly used in other solid tumors. By exploiting the large nuclear size of CTCs, this strategy provides an alternative and more standardized approach for single-cell isolation in tumors lacking specific surface markers.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100447"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145579312","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 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":"2025-12-01","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":"Mapping the stage-specific plasma p53 interactome reveals colorectal cancer progression signatures and therapeutic vulnerabilities","authors":"Raajesh Anand Natarajan ,&nbsp;Siva Kaliyamoorthy ,&nbsp;Vinoth Boopathi ,&nbsp;Jawahar Ramasamy ,&nbsp;Ravikumar Sambandam","doi":"10.1016/j.jlb.2025.100329","DOIUrl":"10.1016/j.jlb.2025.100329","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, yet the molecular changes that occur in the bloodstream as the disease advances remain poorly understood. In particular, how p53—a key tumor suppressor—interacts with circulating proteins at different stages of CRC has not been well characterized. In this discovery-phase study, we analyzed plasma samples from patients with CRC stages I–IV using high-resolution LC–MS/MS. Stage-specific proteins were identified and cross-validated with transcriptomic data, revealing TP53 as a central hub in multiple functional networks. Enrichment analyses highlighted progressive changes in pathways linked to immune surveillance, complement activation, and cellular stress responses. Early-stage disease showed signals consistent with tumor suppression and immune regulation, while advanced stages were enriched in proteins associated with metastasis and therapy resistance. Notably, KLHL40 (Stage I) and FKBP1A (Stage III) emerged as potential stage-specific circulating biomarkers with functional links to p53 signaling. These findings outline a plasma-based molecular map of p53-associated protein networks across CRC progression and point to candidate biomarkers that warrant validation in larger, independent, and longitudinal studies.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100329"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417370","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 World Conference on Lung Cancer (WCLC) 2025","authors":"Nadia Ghazali ,&nbsp;Ana Ortega-Franco ,&nbsp;Diego de Miguel-Perez ,&nbsp;Erick F. Saldanha ,&nbsp;Konstantinos Venetis ,&nbsp;Pasquale Pisapia ,&nbsp;Surbhi Singhal ,&nbsp;Benjamin A. Bleiberg ,&nbsp;Carolina Reduzzi ,&nbsp;Roberto Borea","doi":"10.1016/j.jlb.2025.100449","DOIUrl":"10.1016/j.jlb.2025.100449","url":null,"abstract":"<div><div>The role of liquid biopsy in oncological care continues to expand, with multiple studies presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC 2025). This review summarizes recent advances in liquid biopsy for thoracic oncology, encompassing both non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).</div><div>In early detection and screening, proteomic profiling has identified potential biomarkers predictive of future lung cancer risk. The integration of proteomics with clinical and imaging data can improve pulmonary nodule malignancy prediction. In resectable NSCLC, tumour-informed whole-genome sequencing (WGS) assay demonstrated high sensitivity for minimal residual disease (MRD) detection, with MRD clearance following neoadjuvant osimertinib or chemo-immunotherapy associated with favorable outcomes.</div><div>In advanced NSCLC, longitudinal liquid biopsy analyses reveal dynamic subclonal evolution driving early treatment resistance. Circulating tumor DNA (ctDNA) clearance following targeted therapy in MET exon 14 skipping and BRAF-mutated tumors was associated with improved clinical outcomes. Emerging biomarkers such as ctDNA tumour fraction and circulating microRNA signatures are promising for radiotherapy stratification and prediction of immunotherapy-related toxicities.</div><div>In SCLC, MRD monitoring enables earlier detection of disease progression and supports ctDNA-guided selection of patients for consolidation immunotherapy following chemotherapy. Overall, these advances demonstrate the expanding role of liquid biopsy in improving early detection, guiding treatment, and improving disease monitoring in lung cancer.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100449"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693792","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":"Cerebrospinal fluid ctDNA clarifies clonal divergence: leptomeningeal flare of EGFR-mutant disease after switch to selpercatinib for acquired RET fusion","authors":"Kei Kunimasa ,&nbsp;Motohiro Tamiya ,&nbsp;Takako Inoue ,&nbsp;Nobuaki Mamesaya ,&nbsp;Tsunehiro Tanaka ,&nbsp;Kiyohide Komuta ,&nbsp;Shun Futamura ,&nbsp;Keiichiro Honma ,&nbsp;Kazumi Nishino","doi":"10.1016/j.jlb.2025.100450","DOIUrl":"10.1016/j.jlb.2025.100450","url":null,"abstract":"<div><div>Liquid biopsy can expose spatially segregated resistance biology that is invisible to single-site tissue testing, particularly across the blood–brain barrier. We report how cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) clarified therapeutic direction in <em>EGFR</em>-mutated non-small-cell lung cancer (NSCLC) with leptomeningeal involvement. A 67-year-old woman with <em>EGFR</em> exon 19–deleted adenocarcinoma received afatinib followed by long-term osimertinib. After three years, progression of the primary lesion prompted rebiopsy, which revealed a <em>CCDC6-RET</em> fusion with strong RET immunoreactivity. Selpercatinib monotherapy yielded minor thoracic shrinkage at 1 month but was followed by dizziness and MRI evidence of leptomeningeal enhancement at 3 months. CSF analysis showed pleocytosis without malignant cells. Critically, CSF ctDNA demonstrated the <em>EGFR</em> E746_A750 deletion at 29.2 % variant allele frequency by amplicon sequencing, whereas the <em>CCDC6–RET</em> fusion was undetectable by targeted sequencing and highly sensitive single-plex qPCR using junction-specific primers. Re-challenging with osimertinib rapidly improved symptoms and led to resolution of leptomeningeal enhancement. These data indicate clonal divergence at acquired resistance: a <em>RET</em>-fusion clone dominated the thoracic compartment while <em>EGFR</em>-addicted clones predominated in the leptomeninges. The leptomeningeal flare after discontinuing EGFR inhibition highlights the risk of switching to RET inhibitor monotherapy when CNS disease is driven by the original <em>EGFR</em> mutant clone. CSF liquid biopsy provided actionable, compartment-specific genotyping that outperformed cytology and guided effective retreatment. Incorporating CSF ctDNA into routine evaluation may improve therapeutic alignment across sanctuary sites; when feasible, maintaining EGFR blockade should be considered when CNS involvement is suspected in <em>EGFR</em>-mutated NSCLC in routine practice.</div></div>","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"10 ","pages":"Article 100450"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750061","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":"ALMA platform: a Pan-cancer agnostic multi-modal liquid biopsy approach for enhanced MRD detection and therapy monitoring","authors":"Dr. Lara Paracchini ,&nbsp;Dr. Lorena Ancona ,&nbsp;Dr. Luca Beltrame ,&nbsp;Dr. Sonia Ismari ,&nbsp;Dr. Micaela Piemontese ,&nbsp;Dr. Laura Mannarino ,&nbsp;Dr. Francesca Chemi ,&nbsp;Paolo Zucali (Prof.) ,&nbsp;Paolo Bossi (Prof.) ,&nbsp;Domenica Lorusso (Prof.) ,&nbsp;Dr. Alberto Puccini ,&nbsp;Maurizio D'Incalci (Prof.) ,&nbsp;Dr. Sergio Marchini","doi":"10.1016/j.jlb.2025.100337","DOIUrl":"10.1016/j.jlb.2025.100337","url":null,"abstract":"","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100337"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594427","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":"Repositioning ctDNA as a Real-Time Clinical Compass: A Meta-Analysis of 14,000 Patients Across 42 Studies","authors":"Dr. Mohamed Tharwat Kamouna","doi":"10.1016/j.jlb.2025.100338","DOIUrl":"10.1016/j.jlb.2025.100338","url":null,"abstract":"","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100338"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594514","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":"Comparative evaluation of Circulating Tumor Cell (CTC) enrichment strategies in lung and breast cancers","authors":"Dr. Carlos Pedraz Valdunciel ,&nbsp;Dr. Nadia Bayou ,&nbsp;Dr Ashish Saxena ,&nbsp;Dr Letizia Pontolilo ,&nbsp;Dr Urko del Castillo ,&nbsp;Dr Mara Serena Serafini ,&nbsp;Dr Rafael Rosell (Prof) ,&nbsp;Dr Massimo Cristofanilli (Prof) ,&nbsp;Dr Paraskevi Giannakakou (Prof) ,&nbsp;Dr Carolina Reduzzi","doi":"10.1016/j.jlb.2025.100361","DOIUrl":"10.1016/j.jlb.2025.100361","url":null,"abstract":"","PeriodicalId":101235,"journal":{"name":"The Journal of Liquid Biopsy","volume":"9 ","pages":"Article 100361"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594541","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}