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PubMed2025

Circulating miRNAs and inflammatory markers - Associations between miRNAs and cytokine levels point to miRNA-mediated sCD40L release from platelets.

MicroRNAs (miRNAs) are gaining increasing attention, particularly because of their involvement in immune-related signaling pathways. We investigated the association between 179 plasma-circulating miRNAs (Plasma Focus microRNA PCR Panel) and 47 cytokines ("MILLIPLEX® panel) in 692 participants of the population-based SHIP-TREND cohort (age range 21-79) and two additional cohorts to present a comprehensive map of miRNA-cytokine relations. Multivariate linear regression models identified Bonferroni-corrected significant associations between miRNAs and cytokines for EGF (pro-epidermal growth factor), PDGF-AA, PDGF-AB/BB (platelet-derived growth factor subunit A and B), VEGF-A (vascular endothelia growth factor A), and sCD40L (soluble CD40 ligand) with sCD40L showing the most robust pattern. These models were adjusted for age, sex, platelet count, BMI, smoking, and technical parameters. In the follow-up sample (N = 191, 7 years after initial sampling), we confirmed that the observed associations were stable over time and replicated our findings in an independent clinical cohort (N = 74). Furthermore, the causal mediation results provide evidence for the involvement of platelet activity in the regulation of sCD40L mediated by five miRNAs in the range of 25 %-69 % of the effect being mediated (strongest mediation for hsa-miR-223-3p). Our study highlights a strong and stable miRNA-mediated modulation of sCD40L, at the stage of platelet activation with potential subsequent effects on the interaction of immune cells and haemostasis pointing to a complex regulatory mechanism. Future research is needed to determine the clinical relevance of our observations in the context of vascular thrombosis, immunological disorders, and neurodegeneration.

Humans↗

PubMed2026

Identification of circulating parasite and host biomarkers in the serum proteome of Trypanosoma vivax-infected sheep under immunosuppression.

Bovine trypanosomiasis, caused by Trypanosoma vivax, presents a major threat to livestock health, primarily due to the lack of efficient field diagnostic tools. This study aimed to identify potential parasite and host-derived biomarkers through a longitudinal proteomic analysis of serum from sheep experimentally infected with a T. vivax isolate. Utilizing LC-MS/MS and bioinformatics, 154 proteins were identified, comprising 150 host (Ovis aries) and four pathogen proteins. Principal Component Analysis (PCA) demonstrated a clear separation of samples according to infection stages: Control, Infection (15 parasites/field), and Peak Infection (30-60 parasites/field) Among the parasite proteins, TvY486_0014340, TvY486_0040500, and TvY486_0042480 were identified as candidate antigens for future evaluation. In silico analysis revealed these proteins contain multiple B-cell epitopes with no cross-reactivity to related Trypanosoma species, supporting their potential for immunodiagnostic development. Additionally, three host proteins-folate receptor 3 (FOLR3) and complement components C1QA and C1QC-were significantly modulated across all infection phases. The upregulation of FOLR3 likely reflects a compensatory response to parasite-induced anemia, while the downregulation of C1Q components suggests immune evasion strategies. These findings highlight specific parasite antigens and host regulatory patterns that may serve as candidate biomarkers for the diagnosis and monitoring of T. vivax infection, facilitating the development of improved point-of-care assays.

Animals↗

PubMed2025

Cross-omics risk scores of inflammation markers are associated with all-cause mortality: The Canadian Longitudinal Study on Aging.

Inflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (polygenic risk score [PRS]), metabolomics (metabolomic risk score [MRS]), and epigenetics (epigenetic risk score [ERS]) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). We found that multi-omics risk scores generally outperformed single-omics risk scores in predicting all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher hazard ratio (HR) for all-cause mortality when including both score and circulating IL-6 in the same model (1-SD IL-6 MRS-ERS: HR = 2.20 [1.55-3.13] vs. 1-SD circulating IL-6 HR = 0.94 [0.67,1.32]. 1-SD IL-6 PRS-MRS: HR = 1.47 [1.35,1.59] vs. 1-SD circulating IL-6 HR = 1.33 [1.18, 1.51]. 1-SD PRS-MRS-ERS: HR = 1.95 [1.40, 2.70] vs. 1-SD circulating IL-6: HR = 0.99 [0.71, 1.39]). In the Nurses' Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1 SD of IL-6 PRS and 1-SD IL-6 PRS-MRS had HR = 1.12 [1.00,1.26] and HR = 1.13 [1.01,1.26] among individuals >65 years old without mutual adjustment of the score and circulating IL-6. Our study demonstrates that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for the aging process and lifespan.

Humans↗

PubMed2026

Circulating Tumor DNA in Bladder Cancer: Current Clinical Evidence and Emerging Multi-Omics Perspectives-A Narrative Review.

Background: Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for real-time disease monitoring in muscle-invasive bladder cancer (MIBC). This narrative review summarizes current clinical evidence regarding ctDNA across disease stages. Methods: We examine recent translational and clinical findings, incorporating key prospective data from practice-changing trials, as well as insights into minimal residual disease (MRD) detection, treatment escalation and de-escalation strategies, and systemic barriers to adoption. Results: Postoperative ctDNA positivity consistently identifies patients with molecular residual disease (MRD) who face a substantially higher risk of recurrence and mortality, frequently preceding radiographic relapse by several months. Prospective evidence now validates ctDNA as a predictive biomarker to guide adjuvant immunotherapy escalation, while sustained ctDNA negativity correlates with high long-term disease-free survival. Beyond plasma ctDNA, emerging multi-compartment liquid biopsies-integrating urinary tumor DNA (utDNA)-demonstrate enhanced sensitivity, particularly in bladder-sparing and local surveillance settings. Furthermore, integrating genomic ctDNA profiling with novel post-transcriptional layers like epitranscriptomics offers a functional framework to capture tumor adaptation under therapeutic pressure. However, clinical translation remains constrained by a lack of assay harmonization, variable analytical sensitivity, and the need for standardized intervention thresholds. Conclusions: Longitudinal liquid biopsies are rapidly shifting MIBC management from static, stage-based paradigms toward dynamic, molecularly informed precision oncology. While ctDNA-guided strategies show robust clinical utility, prospective interventional validation and technical standardization are required before widespread routine integration.

biomarkers↗

PubMed2026

MicroRNAs in Veterinary Viral Diseases: A Comprehensive Review from Molecular Mechanisms to Clinical Translation.

MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length, that regulate post-transcriptional gene expression and have emerged as pivotal modulators of host-virus interactions. Veterinary viral diseases continue to pose substantial challenges to animal health, livestock productivity, food security, and public health, particularly due to their zoonotic potential. While miRNA research has advanced considerably, a comprehensive and critically integrated understanding of their biological functions and clinical applications across veterinary viral diseases remains incomplete. This comprehensive critical narrative synthesis addresses four overarching research questions: (1) What conserved and species-specific miRNA-mediated mechanisms govern major veterinary viral diseases? (2) What contextual factors determine antiviral vs. proviral duality? (3) To what extent do circulating miRNA signatures offer diagnostic and prognostic utility? (4) What translational barriers currently prevent clinical implementation, and how can the One Health framework help overcome them? Integrating three interconnected dimensions-molecular mechanisms, pathogen-specific responses, and translational applications-the review synthesizes evidence across PRRSV, avian oncogenic viruses (MDV, ALV), the immunosuppressive IBDV, FMD, BVDV, Ebola, Hendra, Rabies, and aquatic viral diseases. A key contribution of this review is the proposal of a four-axis contextual framework that explains the antiviral/proviral duality of miRNAs, and a 'One miRNA, One Health' convergence model with a concrete implementation roadmap. Key findings include: (a) a four-axis contextual framework (cell type, infection stage, viral strain, host-viral miRNA competition) that explains the antiviral/proviral duality; (b) virus-encoded miRNAs (v-miRNAs) as lower-risk therapeutic targets due to their absence from uninfected host genomes; (c) circulating miRNA biomarkers validated only at proof-of-concept stage (TRL 1-3), with no veterinary product yet at TRL ≥4; and (d) zoonotic conservation of miR-155, miR-146a, miR-21, and miR-122 across human and veterinary pathogens, supporting a 'One miRNA, One Health' convergence strategy. Critical short-term priorities are standardized pre-analytical protocols, open-access veterinary miRNA databases, and multicenter validation in natural infection cohorts.

Antiviral therapy↗

PubMed2026

RNA splicing and cardiovascular disease: a guide for cardiologists.

Alternative splicing (AS) is a fundamental RNA processing mechanism, which generates different RNA transcripts and consequently different protein isoforms from a single gene. This increases the diversity of proteins within an organism and can fine-tune biological processes. This review examines how cardiac-enriched RNA-binding proteins establish heart-specific splicing programs governing aspects of cardiac development, function, and disease. Developmentally, coordinated sarcomeric isoform switches underpin the foetal-to-adult transition and further isoform rewiring in ion channel and kinase genes determine electrophysiology and excitation-contraction coupling. AS contributes to the pathogenesis of several cardiomyopathies and emerging datasets suggest that pathological hypertrophy engages distinct splicing signatures compared with physiological hypertrophy. This review summarizes diagnostic and prognostic opportunities arising from bulk, long-read, and single-cell/nucleus transcriptomics, which resolve cell type-specific isoforms and disease-associated switches. Circulating RNA biomarkers (including splice ratios and circularRNAs) may signify myocardial remodelling and arrhythmic risk. Integrative approaches that link AS with proteomics and genomics improve variant interpretation, reveal previously unannotated protein isoforms, and enable tracking of disease progression and therapy response. Finally, an outline of therapeutic strategies to modulate AS in cardiovascular disease (CVD), including antisense oligonucleotides, small molecules, and genome-editing modalities (CRISPR, base, and prime editing), is provided. The major challenges that remain before splice-targeting therapeutics can be targeted to treat cardiovascular disease are highlighted. Lessons from neuromuscular indications establish clinical feasibility of splicing correction and motivate translation to cardiology. Together, mechanistic insight, biomarker development, and therapeutic innovation position RNA splicing as a tractable axis for precision cardiovascular medicine.

Humans↗

PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗

PubMed2026

Circulating IGF2BP3 enables risk stratification and predicts treatment response in Ewing sarcoma.

Ewing sarcoma (EWS), the second most common pediatric bone tumor, presents with a markedly heterogeneous clinical spectrum and optimal risk stratification is therefore crucial for improving treatment outcomes. The RNA-binding protein IGF2BP3 is a critical oncogenic driver of EWS malignancy. This study evaluates the clinical utility of circulating IGF2BP3 as a biomarker to predict treatment response and risk of disease progression in patients with EWS. Plasma samples from 60 patients with EWS diagnosed and treated at the IRCCS Rizzoli Orthopedic Institute (Bologna, Italy) were collected at diagnosis before treatment initiation and/or after induction chemotherapy. For 51 of these patients, blood was collected at diagnosis, prior to any treatments. For 25 patients, blood samples were available at diagnosis and before surgical intervention, allowing longitudinal analysis in the same patient. For 9 patients, blood was collected only after preoperative chemotherapy, before surgical intervention. Circulating IGF2BP3 levels were quantified using a highly specific and sensitive ELISA assay. Plasma samples from healthy donors served as controls. IGF2BP3 plasma levels were correlated with IGF2BP3 tumor tissue expression, established clinical risk factors, and cumulative incidence of relapse using univariable and multivariable analyses. Plasma IGF2BP3 levels were significantly elevated in patients with EWS compared with healthy controls, with a subset of patients (22/51, 43.2%) exhibiting clinically relevant concentrations. Circulating IGF2BP3 levels reflected tumor expression of the molecule and provided additional prognostic information beyond standard clinicopathologic features. The prognostic impact of circulating IGF2BP3 was primarily observed in patients with localized disease, in whom elevated levels were identified as a significant adverse prognostic factor for disease-specific survival (hazard ratio, 10.63; 95% CI, 1.27-88.62; P = 0.029). Longitudinal monitoring demonstrated that persistence of IGF2BP3 in plasma after induction chemotherapy was a strong predictor of poor clinical outcomes. Circulating IGF2BP3 represents a valuable biomarker for early risk stratification in EWS, particularly in patients with localized disease. Although this is single-marker assay, the expression of the molecule may impact on the fate of many mRNAs. We present an accurate, simple, cost-effective and easy clinical applicable tool to support risk-adapted therapeutic interventions. The limited number of employed patients warrants the need of larger cohorts for validation.

Humans↗

PubMed2026

Research updates in cystic fibrosis related diabetes: Understanding pathophysiology, expanding animal and human islet models, and advancing clinical and translational research.

In 2024-2025, the Cystic Fibrosis Foundation (US) and Cystic Fibrosis Trust (UK) hosted an International CFRD Consortium round-table webinar series for basic science, translational, and clinical researchers with the goal of sharpening mechanistic understanding of CFRD pathogenesis and prioritizing therapeutic development. This review summarizes the research priorities identified in the International CFRD Consortium, including (i) further investigation into the role of pancreatic fibrosis, vascular abnormalities, and α-cell dysfunction in the development of CFRD; (ii) the creation and refinement of novel animal and human cell- and tissue-based models to understand the complex interplay of exocrine and endocrine cells in the CF pancreas; (iii) development and validation of circulating and imaging biomarkers, together with dynamic glucose testing to explore β-cell function and kinetics in people with CF across the dysglycemia spectrum; and (iv) prospective clinical studies to guide CFRD treatment options and investigate the changing landscape of aging, increasing prevalence of obesity and diabetes and their complications in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Collectively, these priorities aim to accelerate transition from mechanism to intervention and expand evidence-based care for people with CF at risk of, or living with, CFRD.

Humans↗

PubMed2026

Genomic, transcriptomic, and molecular predictors of response to neoadjuvant therapy in locally advanced rectal cancer: a narrative review.

Total neoadjuvant therapy (TNT) has emerged as a key treatment paradigm for locally advanced rectal cancer, reducing distant metastasis rates and facilitating organ preservation in selected patients. However, treatment response remains heterogeneous, highlighting the need for biomarkers that can guide treatment selection and optimise outcomes. This narrative review synthesises the current evidence regarding tumour-intrinsic genomic biomarkers associated with response to neoadjuvant therapy, encompassing somatic mutations, germline polymorphisms, gene expression profiles, mismatch repair (MMR) status, protein expression, epigenetic markers, and circulating tumour-derived biomarkers across conventional chemoradiotherapy (CRT) and TNT paradigms. Across the reviewed literature, individual somatic mutations, including KRAS, TP53, and BRAF, demonstrated limited reproducibility as predictive biomarkers, although KRAS mutations were recurrently associated with lower pathological complete response (pCR) rates in CRT-era cohorts. Germline polymorphisms in DNA repair (XRCC1) and folate metabolism (MTHFR) genes showed inconsistent associations with treatment response. In contrast, transcriptomic biomarkers demonstrated greater biological coherence, with proliferative, epithelial-mesenchymal transition, and metabolic signatures frequently associated with treatment resistance, while multi-gene classifiers generally outperformed single-gene markers. Among currently available tumour-intrinsic biomarkers, MMR deficiency was the most consistently reported biomarker associated with reduced response to fluoropyrimidine-based regimens, including TNT, although TNT-specific evidence remains comparatively limited. Dynamic circulating tumour DNA (ctDNA) monitoring, particularly ctDNA clearance during or after therapy, was consistently associated with pathological response and long-term oncologic outcomes across reviewed studies, whereas baseline ctDNA levels showed limited predictive value. Overall, the reviewed literature suggests that biomarker research in rectal cancer has evolved from single-gene analyses towards pathway-level and dynamic biomarkers. The integration of transcriptomic signatures, MMR status, and dynamic ctDNA monitoring may represent a promising strategy for personalising neoadjuvant therapy, improving patient selection for organ-preserving approaches, and enhancing oncologic outcomes in locally advanced rectal cancer. Nevertheless, the evidence base remains heterogeneous, and further prospective validation, assay standardisation, and evaluation within contemporary TNT cohorts are required before these biomarkers can be routinely incorporated into clinical decision-making.

Humans↗

PubMed2024

Identification of biomarkers and potential therapeutic targets for pancreatic cancer by proteomic analysis in two prospective cohorts.

Pancreatic cancer (PC) is the deadliest malignancy due to late diagnosis. Aberrant alterations in the blood proteome might serve as biomarkers to facilitate early detection of PC. We designed a nested case-control study of incident PC based on a prospective cohort of 38,295 elderly Chinese participants with ∼5.7 years' follow-up. Forty matched case-control pairs passed the quality controls for the proximity extension assay of 1,463 serum proteins. With a lenient threshold of p < 0.005, we discovered regenerating family member 1A (REG1A), REG1B, tumor necrosis factor (TNF), and phospholipase A2 group IB (PLA2G1B) in association with incident PC, among which the two REG1 proteins were replicated using the UK Biobank Pharma Proteomics Project, with effect sizes increasing steadily as diagnosis time approaches the baseline. Mendelian randomization analysis further supported the potential causal effects of REG1 proteins on PC. Taken together, circulating REG1A and REG1B are promising biomarkers and potential therapeutic targets for the early detection and prevention of PC.

Humans↗

PubMed2025

Next-generation sequencing in breast cancer: current clinical applications and future directions.

INTRODUCTION: Breast cancer is a heterogeneous disease that claims 670,000 lives by 2022. Omic technologies, particularly next generation sequencing (NGS) offers promising avenues for precision medicine. American Society of Clinical Oncology (ASCO) outlines genomic testing's utility, emphasizing prognostic and diagnostic potential. OBJECTIVES: This review succinctly explores NGS's evolution and clinical applications of NGS in breast cancer, thereby guiding future research to enhance patient care. METHODS: Comprehensive literature searches were conducted using databases such as PubMed, Google Scholar, and ResearchGate, focusing on keywords including breast cancer, HER-2 low breast cancer, circulating tumour DNA, single-cell RNA sequencing, and next-generation sequencing. Peer-reviewed, high-quality articles published in English were selected for inclusion. RESULTS: Previous studies have explored the evolution of NGS technology and its clinical applications in breast cancer, including genomic and transcriptomic characterization, treatment guidance, and resistance prediction. Molecular profiling of challenging entities such as early-onset breast cancer and HER-2 low tumours was summarized, with key findings highlighted. This review also discusses emerging technologies, including circulating DNA and single-cell sequencing, as promising avenues for discovery. CONCLUSION: NGS has revealed the genomic and transcriptomic diversity of breast cancer, identifying actionable alterations associated with chemotherapy response and resistance to therapies such as trastuzumab, TKIs, and CDK4/6 inhibitors. Circulating tumour DNA (ctDNA) shows potential for diagnosis, prediction, prognosis, and monitoring, despite tumour heterogeneity. Single-cell analysis enables exploration of individual cell transcriptomes, though high costs and low throughput remain barriers to widespread adoption. HER2-low tumours continue to pose significant research challenges.

Humans↗

PubMed2026

Integrating Radiogenomics and CSF-Based Liquid Biopsy Sequencing for Precision Neuro-Oncology.

Glioblastoma and diffuse gliomas pose major therapeutic challenges due to marked intratumoral heterogeneity, limited tissue accessibility, and the blood-brain barrier. Tissue-based next-generation sequencing (NGS) remains essential for WHO CNS5 molecular classification, yet it is invasive and poorly suited to serial monitoring. Two complementary non- or minimally invasive approaches have advanced rapidly: radiogenomics, which correlates multiparametric MRI features with genomic alterations, and cerebrospinal fluid (CSF) liquid biopsy sequencing, which detects circulating tumor DNA with high tissue concordance. This review examines the independent progress and synergistic integration of radiogenomics and CSF-NGS. Imaging signatures can non-invasively predict key drivers (IDH1/2, EGFR, TERT, PTEN, TP53) and molecular subtypes, while CSF-ctDNA sequencing enables real-time assessment of clonal evolution, therapy resistance (including post-temozolomide hypermutation), and residual disease. We discuss technical considerations, performance metrics, multimodal artificial-intelligence fusion, and emerging clinical applications for diagnosis, prognosis, treatment selection, and longitudinal surveillance. Critical challenges, standardization, prospective validation, and workflow integration are highlighted. By combining the spatial phenotypic information of radiogenomics with the temporal genomic resolution of CSF sequencing, this multimodal strategy offers a promising path toward precision neuro-oncology and reduced reliance on repeated invasive sampling.

Humans↗

PubMed2026

Associations of neighborhood deprivation with breast cancer tumor genomics, targeted treatment use, and survival.

PURPOSE: Neighborhood environments appear to influence breast cancer biology and outcomes. This study evaluated somatic, treatment, and outcome differences by Area Deprivation Index in patients with metastatic breast cancer. METHODS: Retrospective, population-based cohort study using clinical and genomic data gathered between 2015 and 2024 at four academic institutions in the United States. The outcomes were differences in circulating tumor DNA mutation profiles, PI3K inhibitor use, and survival between patients with metastatic breast cancer living in high deprivation (Area Deprivation Index ≥ 60 by national rank) and low deprivation (< 60) neighborhoods. RESULTS: Among 1127 patients with metastatic breast cancer, 335 (29.7%) lived in high deprivation areas. These patients were more likely to have TP53 mutations (Odds ratio 1.49, 95% Confidence Interval 1.07-2.08, P = 0.018). Among hormone receptor-positive, HER2-negative patients eligible for PI3K inhibitors, those from high deprivation areas were less likely to receive them (17.4% vs. 36.7%, p = 0.02). Median survival from the time of circulating tumor DNA testing was significantly shorter in the high deprivation group (24 months versus 28 months, p = 0.04) and for Black patients in the high deprivation group versus Black patients in low deprivation group and all White patients (15 months versus 25-28 months, p = 0.02). CONCLUSIONS: We found that patients with metastatic breast cancer living in high deprivation neighborhoods were more likely to have TP53 mutations, an indicator of aggressive disease biology, less likely to receive PI3K inhibitors, and had shorter overall survival compared to patients living in low deprivation neighborhoods by Area Deprivation Index.

Humans↗

PubMed2026

Accelerating Lung Cancer Management Through Previsit Liquid Biopsy: Results From the LUNG-FAST Pilot Study.

BACKGROUND: Timely molecular profiling is essential for treatment selection in non-small cell lung cancer (NSCLC), yet delays in biomarker testing remain common. We evaluated the feasibility and early clinical impact of a nurse navigator-driven workflow to initiate liquid biopsy before the initial oncology visit. METHODS: LUNG-FAST (Liquid Biopsy for Urgent Neoplastic Genomic Profiling Focused Accelerated Stratification and Testing) was a 4-month prospective pilot at a tertiary cancer center. Intake nurse navigators identified eligible patients with suspected or newly diagnosed lung cancer and facilitated previsit liquid biopsy ordering. Feasibility, turnaround times, genomic findings, and early clinical outcomes were assessed. RESULTS: Among 64 patients, intake nurse navigators identified 94% (60/64) of eligible cases. Liquid biopsy was ordered in 58 patients, with 62% (36/58) placed before the initial oncology visit. Median turnaround time from blood draw to results was 8.5 days for commercial testing and 12.5 days for institutional testing. FDA-actionable genomic alterations were identified in 34% (22/64) of patients, while an additional 11% (7/64) harbored clinically relevant, non-FDA-actionable alterations. Overall, FDA-actionable or clinically relevant alterations were identified in 45% (29/64), with 22% detected by liquid biopsy and an additional 23% by tissue-only profiling. Median time from new patient visit to systemic therapy was 26 days. CONCLUSIONS: A nurse navigator-driven workflow enabling previsit liquid biopsy is feasible and identifies actionable genomic alterations in a substantial proportion of patients with lung cancer. Plasma and tissue profiling are complementary, and earlier plasma-based testing may expedite treatment decision-making while highlighting opportunities to optimize biomarker testing workflows.

Humans↗

PubMed2026

Establishment of a multi-targeted magnetic combined enrichment system for circulating tumor cells in gastric cancer and analysis of their genomic profiles.

Background: This study aims to establish an efficient Circulating tumor cells (CTCs) multi-targeted magnetic combined sorting system for Gastric cancer (GC), while comparing it with tissue and circulating tumor DNA (ctDNA) samples to evaluate its feasibility and consistency for genomic profiling analysis. Method: Establish an efficient CTCs sorting system for GC targeting epithelial cell adhesion molecule, cell surface vimentin, and protein tyrosine kinase 7, and evaluate its physicochemical properties and cell capture efficiency. Assess the feasibility of tumor cell detection through animal experiments. Sixty-eight GC patients underwent CTCs detection. Clinical information was analyzed to evaluate the clinical utility of CTCs in the auxiliary diagnosis of GC. Next-generation sequencing was performed on GC tissue, CTCs, and ctDNA samples to assess the consistency of genetic mutations across different sample types. Results: The constructed CTCs sorting system exhibits excellent physicochemical properties, achieving a capture rate of 94.68%. Animal studies confirm a positive correlation between tumor cells count and tumor volume. The number of CTCs in the blood of GC patients is significantly correlated with tumor size, stage, and metastasis. The CTCs count in GC patients is significantly higher than in healthy individuals and high-risk groups for cancer, with diagnostic sensitivity and specificity of 97.29% and 97.73%, respectively. The mutation detection rate in CTCs samples was significantly higher than that in tissue and ctDNA samples. The concordance rate between CTCs and tissue mutations was 24.32%, while the concordance rate between CTCs and ctDNA mutations was 19.05%. Conclusion: This study successfully established a multi-target combined CTCs multi-targeted magnetic combined sorting system for GC. CTCs detection based on this system can be used for the auxiliary diagnosis of GC patients. Furthermore, compared to GC tissue and ctDNA samples, CTCs detection enables more comprehensive genomic profiling analysis and serves as an important supplement to GC genomic analysis.

Humans↗

PubMed2026

An alignment-free strategy for circulating tumor DNA detection and tumor fraction estimation from whole-genome sequencing data.

Circulating tumor DNA (ctDNA) is emerging as a promising biomarker for postoperative monitoring of cancer patients. Precise estimation of circulating tumor fraction is crucial for evaluating treatment effects and timely detection of disease recurrence. All current ctDNA detection methods that utilize whole-genome sequencing (WGS) data rely on the reference genome alignment of sequencing reads and often apply separate tools for detecting different variant types. However, various bioinformatic analysis confounders and the application of external variant calling tools could be avoided by analyzing k-mers from unaligned sequencing reads. While k-mer-based methods have successfully been applied for somatic variant validation and detection, the potential of k-mer-based ctDNA detection is unexplored. We have developed a tumor-informed alignment-free ctDNA detection tool called ctDNAmer that detects tumor-specific somatic variation directly from unaligned sequencing data by identifying k-mers unique to the tumor DNA. ctDNAmer detects variant information across the genome by comparing the primary tumor and germline WGS data and accounts for sample-specific germline variability and technical noise in the same framework. We tested the utility of ctDNAmer for tumor fraction estimation on postoperative plasma cfDNA WGS data (mean sequencing depth ~ 28x) from 90 stage III colorectal cancer patients with three years of follow-up. The tumor fraction (TF) estimates agreed with the available clinical information and ctDNA was detected in 77% (17/22) of recurring patients with a median lead time of 8 months compared to radiological imaging. We further validated ctDNAmer's tumor fraction estimates based on a comparison with the mean cfDNA allele frequencies of somatic clonal SNVs identified from aligned primary tumor sequencing data. The TF estimates showed a strong Pearson correlation of 0.897 with the mean allele frequencies and improved ctDNA detection results across samples with an AUC of 0.79 compared to 0.75 if the mean allele frequency of clonal mutations is used.

Circulating Tumor DNA↗

PubMed2026

Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.

OBJECTIVES: To determine whether the reported 0%-70% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification. METHODS: We conducted a PRISMA 2020-compliant systematic review of observational studies (January 1, 2000-May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context-integrated framework to classify methodological robustness and discordance. RESULTS: Fourteen studies were included (57% high-income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one-third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single-marker studies (mostly 0%-7.1%, with outliers ~50%-70%) and 6.9%-53% in multi-marker studies. Discordance was substantial and greater in LMIC settings than HIC. CONCLUSION: Current diagnostic approaches in SCD appear method-dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251087800.

Humans↗