J Liq Biopsy. 2026 Sep 19;14:100496. doi: 10.1016/j.jlb.2026.100496. eCollection 2026 Dec.

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) analysis has revolutionized minimal residual disease (MRD) monitoring, but conventional tumor-informed amplicon-based sequencing (AMP) is limited by the narrow variant capacity and diversity. Hybrid capture-based sequencing (HYB) is more versatile and enables both tumor-informed and tumor-naïve liquid biopsy profiling.

METHODS: We analytically validated the performance of our novel HYB workflow and VarSURE variant calling pipeline, using reference standards (n = 6), plasma samples of cancer patients (n = 75) and healthy donors (n = 90). Genome-wide (GW) non-mutation features including copy number alterations, fragmentomics, and end-motif signatures were also evaluated to enhance ctDNA-MRD detection. Clinical performance was directly compared against our legacy AMP method (K-TRACK, Gene Solutions), using pre-treatment blood samples across multiple cancers (n = 290) and longitudinal cohorts of colorectal cancer (CRC, n = 64), and hepatocellular carcinoma (HCC, n = 47).

RESULTS: Optimal parameters to maximize assay performance included single-stranded DNA ligation technology, cfDNA input ≥ 15 ng, post-UMI sequencing depth ≥ 2500X, and high number of tracked mutations. In the tumor-informed setting, the HYB workflow was modestly better than the AMP method in detection of pre-treatment ctDNA; addition of GW features was marginally beneficial except in lung cancer. Surveillance ctDNA determined by the HYB workflow had superior sensitivity to predict recurrence in both CRC (AMP: 90.0%, HYB: 100%) and HCC (AMP: 80.0%, HYB: 96.0%). In the tumor-naïve setting, the performance gap widened significantly, and the combined HYB and GW workflow showed the highest performance in baseline ctDNA detection across all cancers, and achieved sensitivity of 90.0% and 92.0% to detect recurrence in CRC and HCC respectively.

CONCLUSIONS: The new methodology offers a streamlined and scalable solution for both comprehensive liquid biopsy profiling and longitudinal MRD tracking in routine clinical practice.

PMID:42830887 | PMC:PMC13634064 | DOI:10.1016/j.jlb.2026.100496

BJS Open. 2026 Sep 4;10(5):zrag142. doi: 10.1093/bjsopen/zrag142.

ABSTRACT

BACKGROUND: Non-operative management after total neoadjuvant therapy (TNT) has emerged as a potential strategy for patients with locally advanced rectal cancer (LARC) achieving clinical complete response (cCR). Circulating tumour DNA (ctDNA) has been proposed as a systemic biomarker to augment response assessment, but its role in predicting cCR and local regrowth remains uncertain.

METHODS: A systematic review and meta-analysis were performed of studies evaluating ctDNA dynamics in patients with LARC undergoing TNT. PubMed, EMBASE, and Web of Science databases were searched from database inception to 31 March 2026. Primary outcomes were the association between post-TNT ctDNA status and cCR and sustained cCR. Pooled odds ratios (ORs) were calculated using a random-effects model.

RESULTS: Six studies comprising 597 patients were included. ctDNA negativity following TNT was associated with higher likelihood of cCR (OR 8.01; 95% confidence interval (c.i.) 1.43 to 44.90; I2 = 27.0%). The association with sustained cCR was not statistically significant (OR 3.46; 95% c.i. 0.03 to 394.64; I2 = 59.9%). Across studies, post-TNT ctDNA positivity was associated with inferior disease-free, distant recurrence-free, and progression-free survival. ctDNA demonstrated high specificity and positive predictive value for residual disease, but low sensitivity for the detection of residual local disease and local regrowth, with a substantial proportion of patients with residual tumour remaining ctDNA negative at restaging.

CONCLUSION: Post-TNT ctDNA positivity may identify patients at increased risk of adverse oncological outcomes. However, ctDNA negativity was not consistently associated with the absence of residual local disease, limiting its utility as an independent determinant of organ preservation eligibility. ctDNA should be interpreted as a complementary tool for systemic risk stratification alongside established anatomical assessment.

PMID:42832577 | DOI:10.1093/bjsopen/zrag142

Cancer Sci. 2026 Oct 5:10.1111/cas.70552. doi: 10.1111/cas.70552. Online ahead of print.

ABSTRACT

Biliary tract cancer (BTC) is a rare abdominal cancer with poor prognosis. Circulating tumor DNA (ctDNA) analysis with liquid biopsy offers a minimally invasive approach for cancer detection and disease monitoring. Given limited reports, this study aims to evaluate minimal residual disease (MRD) and longitudinal ctDNA monitoring in BTC patients. A total of 124 BTC patients were enrolled, with 111 evaluable for ctDNA analysis using a tumor-informed approach. Baseline tumor tissue and plasma samples were collected for comprehensive genomic profiling (CGP). A customized ctDNA panel was developed based on CGP of resectable BTC tumors and public genomic databases for MRD assessment and longitudinal monitoring. ctDNA sequencing was performed using ultradeep targeted next-generation sequencing. Associations between ctDNA detection and outcomes were analyzed. Preoperative ctDNA detection was associated with advanced pathological stage and significantly worse relapse-free survival (RFS) and overall survival. Using this ctDNA panel, preoperative ctDNA was detected in 51.4% of cases, with TP53, KRAS, ARID1A, and SMAD4 being the most frequently mutated genes. During longitudinal monitoring, 57.8% of patients showed persistent ctDNA positivity or subsequent ctDNA detection before radiological recurrence. RFS was significantly shorter among patients with ctDNA positivity during longitudinal monitoring than among those with undetectable ctDNA (HR = 9.04; 95% CI, 3.56-23.97; p < 0.001). Our customized panel detected BTC-specific mutations in plasma using liquid biopsy, and ctDNA positivity was strongly associated with recurrence and survival outcomes. This panel has the potential to improve MRD assessment and longitudinal monitoring in BTC, enabling earlier intervention and improved patient stratification.

PMID:42831344 | PMC:PMC13636022 | DOI:10.1111/cas.70552

J Liq Biopsy. 2026 Sep 19;14:100496. doi: 10.1016/j.jlb.2026.100496. eCollection 2026 Dec.

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) analysis has revolutionized minimal residual disease (MRD) monitoring, but conventional tumor-informed amplicon-based sequencing (AMP) is limited by the narrow variant capacity and diversity. Hybrid capture-based sequencing (HYB) is more versatile and enables both tumor-informed and tumor-naïve liquid biopsy profiling.

METHODS: We analytically validated the performance of our novel HYB workflow and VarSURE variant calling pipeline, using reference standards (n = 6), plasma samples of cancer patients (n = 75) and healthy donors (n = 90). Genome-wide (GW) non-mutation features including copy number alterations, fragmentomics, and end-motif signatures were also evaluated to enhance ctDNA-MRD detection. Clinical performance was directly compared against our legacy AMP method (K-TRACK, Gene Solutions), using pre-treatment blood samples across multiple cancers (n = 290) and longitudinal cohorts of colorectal cancer (CRC, n = 64), and hepatocellular carcinoma (HCC, n = 47).

RESULTS: Optimal parameters to maximize assay performance included single-stranded DNA ligation technology, cfDNA input ≥ 15 ng, post-UMI sequencing depth ≥ 2500X, and high number of tracked mutations. In the tumor-informed setting, the HYB workflow was modestly better than the AMP method in detection of pre-treatment ctDNA; addition of GW features was marginally beneficial except in lung cancer. Surveillance ctDNA determined by the HYB workflow had superior sensitivity to predict recurrence in both CRC (AMP: 90.0%, HYB: 100%) and HCC (AMP: 80.0%, HYB: 96.0%). In the tumor-naïve setting, the performance gap widened significantly, and the combined HYB and GW workflow showed the highest performance in baseline ctDNA detection across all cancers, and achieved sensitivity of 90.0% and 92.0% to detect recurrence in CRC and HCC respectively.

CONCLUSIONS: The new methodology offers a streamlined and scalable solution for both comprehensive liquid biopsy profiling and longitudinal MRD tracking in routine clinical practice.

PMID:42830887 | PMC:PMC13634064 | DOI:10.1016/j.jlb.2026.100496

Genes Dis. 2026 May 17;14(2):102243. doi: 10.1016/j.gendis.2026.102243. eCollection 2027 Feb.

NO ABSTRACT

PMID:42831172 | PMC:PMC13634571 | DOI:10.1016/j.gendis.2026.102243

Biochem Biophys Res Commun. 2026 Sep 30;838:154646. doi: 10.1016/j.bbrc.2026.154646. Online ahead of print.

ABSTRACT

Mitophagy, a selective form of autophagy, has been implicated in tumor progression and therapeutic resistance; however, its prognostic significance in hepatocellular carcinoma (HCC) remains unclear. In this study, we comprehensively evaluated the role of mitophagy-related genes in HCC using multi-omics data. Gene expression profiles were obtained from the TCGA-LIHC and GSE14520 cohorts, and mitophagy-related genes were retrieved from the GeneCards database. Twenty differentially expressed mitophagy-related genes with prognostic value (pDEMGs) were identified, and consensus clustering stratified HCC patients into two clusters with significantly different survival outcomes (P = 0.001). A mitophagy enrichment score (MIES) was then calculated using single-sample gene set enrichment analysis (ssGSEA). Elevated MIES was associated with poorer overall survival (HR = 2.17, P = 0.005), metabolic activation, immune suppression, and differential drug sensitivity. Single-cell analysis of the GSE140228 dataset revealed heterogeneous MIES activity across cell populations, with relatively higher enrichment observed in proliferating T cells and dendritic cells. A six-gene prognostic signature (ACTR6, GAPDH, ATIC, ANP32E, CCT6A, and BSG) was developed using LASSO-Cox regression, which effectively stratified patients into high- and low-risk groups with distinct overall survival outcomes (1-, 3-, and 5-year AUCs: 0.780, 0.682, and 0.690, respectively). The risk score was correlated with immune infiltration patterns, mutational landscape, and chemotherapy response. qPCR validation further confirmed the upregulation of ACTR6, CCT6A, ATIC, and BSG in HCC cells. Collectively, these findings establish a mitophagy-related scoring system that reflects immune and genomic characteristics, as well as a six-gene signature with independent prognostic value, highlighting the potential clinical relevance of mitophagy in HCC.

PMID:42828884 | DOI:10.1016/j.bbrc.2026.154646

Epigenomics. 2026 Oct 3:1-13. doi: 10.1080/17501911.2026.2740396. Online ahead of print.

ABSTRACT

Plasma cell-free DNA (cfDNA) is fragmented nonrandomly, reflecting the chromatin architecture of its source cells and the nucleases that process it. The fragmentome can therefore provide an indirect readout of cellular regulatory state. This review examines how DNA methylation, chromatin accessibility, nucleosome positioning, protein occupancy, and nuclease activity shape cfDNA fragmentation and considers their implications for oncology. We organize fragmentomic measurements into four classes: coverage and protection, fragment size, fragment-end properties, and diversity and entropy metrics. We discuss the genomic contexts in which these features are informative, including repetitive and transposable elements, and compare platforms by sequencing requirements, feature portability, and the fragment populations captured by different library chemistries. We then review applications in cancer screening, tissue-of-origin inference, molecular subtyping, prognosis, minimal residual disease detection, and treatment response monitoring. A central challenge for clinical translation is attributing fragmentomic changes to their tissue of origin.

PMID:42829334 | DOI:10.1080/17501911.2026.2740396

Clin Chim Acta. 2026 Oct 3:122873. doi: 10.1016/j.cca.2026.122873. Online ahead of print.

ABSTRACT

Liquid biopsy is a minimally invasive approach to early detection and biomarker assessment in gynecological cancers. This structured review synthesizes evidence on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomal non-coding RNAs, epigenetic markers (methylation and fragmentation), and multi-omics signatures across ovarian, endometrial, cervical, vulvar, and vaginal malignancies. A structured search of PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library identified studies evaluating early detection, predictive and prognostic performance, therapy monitoring, minimal residual disease (MRD) detection, resistance mechanisms, and clinical implementation; each quantitative estimate was assigned an evidence tier reflecting study design and validation status. Multi-omics integration outperforms single-analyte approaches, with a prospective gynecological cohort reporting approximately 82% sensitivity at 97-99% specificity. ctDNA methylation and fragmentomics exceed CA125 in ovarian and endometrial cancers, and cfHPV-DNA shows high specificity in cervical disease. ctDNA dynamics are associated with PARP inhibitor response, MRD status and BRCA reversion-mediated resistance, and detect recurrence before imaging. Reported hazard ratios vary widely but differ in cohort, assay platform and sampling timepoint, and are not directly comparable. Almost all detection estimates derive from retrospective or case-control designs that overestimate performance, and none has been externally and prospectively validated; circulating HPV DNA in cervical cancer is the only marker with prospective trial-level prognostic support. No liquid biopsy assay holds an FDA or EMA indication for any gynecological cancer; pan-tumor clearances exist, but no gynecology-specific companion diagnostic, and no major oncology society recommends use outside clinical trials. Liquid biopsy complements but cannot replace tissue biopsy for diagnosis, subtyping and grading. Randomized trials controlling for lead-time bias are required to establish clinical utility.

PMID:42829044 | DOI:10.1016/j.cca.2026.122873

J Liq Biopsy. 2026 Sep 18;14:100501. doi: 10.1016/j.jlb.2026.100501. eCollection 2026 Dec.

ABSTRACT

INTRODUCTION: Circulating tumor DNA (ctDNA) is a valuable tool for assessing minimal residual disease (MRD) and predicting recurrence in resected non-small cell lung cancer (NSCLC) patients. Combining ctDNA-detection with radiological tumor volume may improve risk stratification.

METHODS: Patients with stage I-III resectable NSCLC were prospectively enrolled in the RESIDUAL study. Plasma samples were collected before surgery (T0), at landmark (10 days after surgery), during surveillance (T2, 20 days, T3, 1 months after surgery and every 3 months for the first year and then at the end of the second year after surgery), and at relapse. Samples were analyzed using Guardant Reveal, a tissue-free methylation-based ctDNA assay. Receiver operating characteristic analysis associated T1 ctDNA status with tumor volume; volume thresholds were calculated via Youden's J, and Cox regression analysis was performed.

RESULTS: Forty-eight patients were enrolled (median age 72 years; 64.6% male). Most had stage I disease (54.2%) and adenocarcinoma histology (79.2%). Median follow-up was 41.8 months, and 19 patients (39.6%) relapsed. Overall ctDNA detection rate was 15.2% across all timepoints. Pre-surgical ctDNA detection was higher in squamous histology and stage II-III disease and was associated with worse disease-free survival (DFS; p = 0.022). Landmark MRD detection was also associated with worse DFS (p = 0.024). Serial surveillance sampling anticipated radiologic recurrence by a median of 2.6 months (range 2.0-7.5). Patients with tumor volume >26,378 mm³ had a significantly higher relapse risk (p < 0.001).

CONCLUSIONS: MRD detection in NSCLC resected patients predicts relapse and poor outcome; integrating ctDNA with tumor volume enhances identification of high-risk patients.

PMID:42828040 | PMC:PMC13631347 | DOI:10.1016/j.jlb.2026.100501

Diabetologia. 2026 Oct 3. doi: 10.1007/s00125-026-06884-2. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Chromatin remodelling is critical for maintaining pancreatic beta cell identity and function, yet the key regulatory mechanisms remain incompletely defined. This study aimed to investigate the role of the switch/sucrose non-fermentable (SWI/SNF) complex subunit BAF60A in preserving beta cell fate and glucose homeostasis.

METHODS: Pdx1-Cre-mediated BAF60A-knockout (BaBKO) and BAF60A-overexpressing (BaBOE) mice, together with tamoxifen-inducible adult beta cell-specific Smarcd1 knockout (BaBKO^TM) and Isl1 knockout (Isl1BKO^TM) mice, were generated to evaluate the role of BAF60A in vivo. Glucose homeostasis was assessed through glucose tolerance tests, insulin tolerance tests and glucose-stimulated insulin secretion (GSIS) assays. Multiomic analyses, including RNA-seq, ATAC-seq, Cleavage Under Targets and Tagmentation (CUT&Tag) and single-cell RNA-seq, were performed to characterise chromatin accessibility and transcriptional changes. BAF60A-interacting proteins were identified with biotin identification (BioID) and GST pull-down assays. Beta cell lineage tracing was used to assess changes in cell identity. In addition, BAF60A and the dedifferentiation marker ALDH1A3 were examined in pancreatic islets from individuals with and without type 2 diabetes.

RESULTS: BaBKO mice exhibited significant glucose intolerance, impaired GSIS and pronounced loss of beta cell identity, accompanied by the acquisition of non-beta endocrine features. Inducible deletion of Smarcd1 in adult beta cells similarly impaired beta cell maturation and promoted dedifferentiation, as confirmed by lineage tracing. BAF60A deficiency reduced enhancer accessibility and downregulated beta cell identity genes. Mechanistically, BAF60A physically interacts with the transcription factor islet-1 (ISL1) to regulate transcription of target genes. Adult beta cell-specific Isl1 deletion recapitulated key features of BAF60A deficiency and abolished the beneficial effect of BAF60A overexpression on insulin secretion. Conversely, BaBOE mice exhibited improved glucose tolerance and enhanced GSIS under high-fat diet conditions. Adeno-associated virus-mediated BAF60A overexpression markedly reduced beta cell dedifferentiation in BKS-db/db mice. In human type 2 diabetes islets, BAF60A expression was significantly reduced and inversely correlated with ALDH1A3.

CONCLUSIONS/INTERPRETATION: This work establishes BAF60A-ISL1-dependent chromatin remodelling as a key mechanism that preserves beta cell identity and function under metabolic stress, providing mechanistic insight into beta cell failure in type 2 diabetes.

PMID:42829354 | DOI:10.1007/s00125-026-06884-2

Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.

PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085

Nat Med. 2026 Oct 2. doi: 10.1038/s41591-026-04673-3. Online ahead of print.

ABSTRACT

Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.

PMID:42827132 | DOI:10.1038/s41591-026-04673-3

Clin Chim Acta. 2026 Oct 2;594:122871. doi: 10.1016/j.cca.2026.122871. Online ahead of print.

ABSTRACT

Head and neck cancers (HNCs) represent one of the most prevalent and lethal types of cancer, accounting for 4.7% of annual cancer new cases and 4.9% of cancer-related mortalities. These high prevalence and mortality rates have positioned HNCs as a global health issue. Despite advances in disease treatment methods, the prognosis of patients with advanced or recurrent diseases remains poor. The difficulty of early-stage diagnosis of HNCs is one of the primary contributors to this reduced long-term survival. Currently available diagnostic and disease-monitoring tools, such as tissue biopsy and imaging techniques, are associated with several limitations, including invasiveness, limited repeatability, and limited sensitivity for detecting minimal residual disease (MRD) and microscopic metastases. In recent years, liquid biopsy has emerged as a promising approach, enabling minimally invasive detection of tumor-related biomarkers in body fluids. This review aims to provide a comprehensive overview of the progress and pitfalls of liquid biopsy in the context of HNCs. In this regard, we discuss the principles of liquid biopsy, applicable biomarker types, sample sources, and advanced detection methods. Furthermore, the current status of liquid biopsy in clinical trials of HNCs and the challenges of its clinical translation are also comprehensively explored.

PMID:42826825 | DOI:10.1016/j.cca.2026.122871

J Bone Oncol. 2026 Sep 16;61:100803. doi: 10.1016/j.jbo.2026.100803. eCollection 2026 Dec.

ABSTRACT

Osteosarcoma relapse surveillance remains dominated by scheduled imaging because salvage treatment depends on anatomical confirmation of pulmonary, local or extrapulmonary recurrence. However, radiological recurrence may occur after a biologically active phase in which residual viable disease or micrometastatic progression is already present but not yet localizable. This clinical-translational review reframes postoperative osteosarcoma surveillance as an action-linked decision workflow rather than a comparison of isolated biomarker technologies. Current evidence suggests that tumor-informed circulating tumor DNA (ctDNA) sequencing provides the strongest osteosarcoma-specific minimal residual disease (MRD) signal, with postoperative positivity associated with inferior event-free survival and, in selected patients, molecular detection preceding imaging-confirmed relapse or progression. Cell-free DNA methylation may offer a mutation-independent adjunct, whereas circulating tumor cells, extracellular vesicles and circulating microRNAs remain exploratory signals without validated postoperative surveillance actions. Chest computed tomography (CT) and local magnetic resonance imaging (MRI) remain indispensable for disease localization and treatment planning, while diffusion-weighted imaging, dynamic contrast-enhanced MRI and radiomics currently provide mainly local viability or risk-enrichment information rather than proven surveillance-intervention evidence. The near-term role of integrated biomarkers is therefore not to replace guideline-based imaging, but to define protocolized pathways for molecular-positive/imaging-negative, imaging-positive/molecular-negative, concordant high-risk and concordant low-risk states. Future studies should test whether biomarker-triggered reassessment improves clinically meaningful outcomes, including resectability, second complete remission, clinical trial access, patient burden and survival, rather than simply documenting recurrence earlier.

PMID:42824543 | PMC:PMC13628598 | DOI:10.1016/j.jbo.2026.100803

Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.

PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085

Clin Gastroenterol Hepatol. 2026 Oct 1:S1542-3565(26)00737-8. doi: 10.1016/j.cgh.2026.09.034. Online ahead of print.

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide, yet most affected individuals remain undiagnosed, and pathways for non-invasive risk stratification and linkage to specialty care remain inconsistently implemented. With the emergence of pharmacologic therapies for metabolic dysfunction-associated steatohepatitis (MASH), accurate patient identification, disease staging, treatment selection, and longitudinal monitoring have become increasingly consequential. In this narrative review, we examine the evolving role of artificial intelligence (AI) across three levels of MASLD care, defined by where an AI output informs a decision and who acts on it: the individual patient, the health system, and health policy. At the patient level, machine-learning and deep-learning approaches have demonstrated potential applications in fibrosis assessment, histopathologic and imaging interpretation, multi-omics integration, treatment-response prediction, and hepatocellular carcinoma risk stratification. Across selected datasets, several models have performed comparably to or better than conventional non-invasive tests and expert interpretation, although no validated tool currently predicts treatment response before therapy. At the health-system level, AI may support population-level case finding, extraction of clinically relevant information from unstructured health records, prognostic assessment, and more efficient allocation of confirmatory testing and specialty care. At the policy level, AI-informed disease-burden modeling and risk stratification may help guide decisions regarding workforce capacity, resource allocation, reimbursement, and treatment coverage. However, most available studies are retrospective, frequently originate from single centers, and have limited external validation. No randomized trial has yet demonstrated that AI-guided management improves clinical outcomes in MASLD, while governance, transparency, and equity frameworks remain underdeveloped. Realizing the clinical value of AI will require prospective multicenter studies embedded within clearly defined MASLD care decisions, validation across genetically and socioeconomically diverse populations and health-system settings, standardized reporting and risk-of-bias assessment, and sustained attention to implementation, governance, and equity.

PMID:42822578 | DOI:10.1016/j.cgh.2026.09.034

World J Urol. 2026 Oct 1;44(1):722. doi: 10.1007/s00345-026-06790-7.

ABSTRACT

PURPOSE: To critically appraise circulating tumour DNA (ctDNA) and extrachromosomal DNA (ecDNA) in prostate and bladder cancer, and to define what evidence links the two.

METHODS: Narrative review of search period July-September 2026, supplemented by reference-list and citation screening, covering ctDNA and ecDNA biology, detection and clinical application in prostate and urothelial cancer. The ctDNA-ecDNA interface was appraised using a five-tier evidentiary framework (copy-number gain; structural rearrangement; amplicon-graph reconstruction; phasing/optical mapping; orthogonal validation).

RESULTS: In bladder cancer, the phase 3 IMvigor011 trial validated ctDNA-guided adjuvant atezolizumab (disease-free survival [DFS] HR 0.64; overall survival [OS] HR 0.59), while persistently ctDNA-negative patients had 2-year DFS/OS of 88.4%/97.1% without adjuvant therapy. In prostate cancer, ctDNA positivity and androgen-receptor alterations are strongly prognostic (median OS 29.0 vs. 47.4 months; HR 2.0), but no prospective ctDNA-guided interventional trial exists. ecDNA is present in approximately 36% of urothelial carcinomas and drives oncogene amplification, heterogeneity, immune evasion and resistance. Evidence linking the two is indirect and asymmetric: prostate cancer offers stronger longitudinal ctDNA evidence via plasma AR-ecDNA proxy signatures, whereas bladder cancer shows stronger structural evidence from urinary sediment; no structurally validated blood ecDNA has been reported. This evidence derives predominantly from metastatic cohorts (mCRPC, post-cystectomy bladder cancer), with no established role in earlier-stage or minimal-residual-disease settings.

CONCLUSION: ctDNA is clinically actionable in bladder cancer and prognostic in advanced prostate cancer, whereas ecDNA remains an investigational driver. Structural confirmation of ecDNA in blood, assay standardisation and prospective biomarker-stratified trials are the priorities for the field.

PMID:42823553 | DOI:10.1007/s00345-026-06790-7

Cancer Treat Res Commun. 2026 Oct 1;49:101463. doi: 10.1016/j.ctarc.2026.101463. Online ahead of print.

ABSTRACT

Liquid biopsy has transformed the management of non-small cell lung cancer (NSCLC). However, current plasma-based approaches face inherent limitations in early-stage and low-burden disease, where tumour-derived DNA fractions are frequently below reliable detection thresholds. As lung cancer care shifts toward earlier detection and minimal residual disease assessment, these constraints expose a critical gap in tumour-proximal molecular sampling. This has prompted growing interest in organ-specific liquid biopsy strategies designed to interrogate biological compartments closer to the site of tumour origin. Exhaled breath condensate (EBC), a non-invasive and lung-derived matrix containing airway lining fluid, represents a biologically rational candidate for such an approach. Emerging translational studies demonstrate the feasibility of detecting tumour-associated genomic alterations and nucleic acids within EBC, suggesting potential utility in early detection, molecular profiling, and longitudinal monitoring. However, substantial challenges remain, including pre-analytical standardisation, analytical validation, and prospective clinical evaluation. This narrative review examines the conceptual rationale for lung-specific liquid biopsy, summarises the evolving evidence supporting EBC, and outlines critical and translational steps required to determine whether EBC can become an integral component of lung cancer diagnostics.

PMID:42822136 | DOI:10.1016/j.ctarc.2026.101463

Front Digit Health. 2026 Sep 16;8:1851723. doi: 10.3389/fdgth.2026.1851723. eCollection 2026.

ABSTRACT

Artificial intelligence (AI) is being applied across diagnostic and therapeutic workflows in hepatology. This narrative review summarizes recent advances in AI for liver disease. In medical imaging and digital pathology, computer vision enables automated quantitative analysis of ultrasound, CT, MRI, and histologic images, with the aim of improving the consistency of lesion detection, disease staging, and prognostic assessment. In biomarker research, machine learning can analyze high-dimensional liquid-biopsy and multi-omics data to develop diagnostic and prognostic models; some have outperformed conventional markers in their study cohorts. Electronic health records (EHRs) and large language models (LLMs) are also being investigated for clinical decision support and personalized management. However, most reported evidence remains retrospective, and clinical adoption is limited by data heterogeneity, poor interpretability, uncertain generalizability, and regulatory requirements. Progress will require standardized datasets, external and prospective validation, clinically relevant endpoints, and human-centered implementation before gains in model performance can be translated into better patient outcomes.

PMID:42819088 | PMC:PMC13624904 | DOI:10.3389/fdgth.2026.1851723

Chem Biodivers. 2026 Oct;23(10):e71778. doi: 10.1002/cbdv.71778.

ABSTRACT

Pancreatic cancer has a dismal prognosis and limited therapeutic options, highlighting an urgent need for effective treatments. Sophoricoside (SOP), a natural isoflavone glycoside, has exhibited anticancer activities in multiple malignancies, including lung cancer, glioblastoma, and hepatocellular carcinoma. We combined cellular assays, network pharmacology, machine learning, and multi-omics to investigate SOP's effects. SOP-inhibited proliferation of MIA PaCa-2, SW1990, and PANC-1 cells dose-dependently. Network pharmacology revealed 85 overlapping targets enriched in MAPK, apoptosis, and PD-L1/PD-1 pathways. Machine learning and differential expression identified PTPN1 as the core target. PTPN1 was markedly upregulated in pancreatic adenocarcinoma, and its high expression correlated with poor survival and immune infiltration. Functional enrichment linked PTPN1 to TGF-β, VEGF, and metabolic reprogramming. Molecular docking suggested a possible binding mode between SOP and PTPN1, involving four predicted hydrogen bonds. SOP reduced PTPN1 mRNA, and PTPN1 knockdown phenocopied SOP's antiproliferative effect with no additivity upon combination. Collectively, this first report demonstrates that SOP restrains pancreatic cancer cell proliferation, with PTPN1 identified as a key functionally required downstream mediator based on integrative computational and functional evidence. This work offers an integrated strategy for mechanistic exploration and highlights PTPN1 as a promising therapeutic biomarker and target for pancreatic cancer.

PMID:42814531 | PMC:PMC13626263 | DOI:10.1002/cbdv.71778