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

Adv Sci (Weinh). 2026 Sep 27:e78005. doi: 10.1002/advs.78005. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) patients show heterogeneous responses to immune checkpoint inhibitors (ICIs). This study developed ECOS-Net, a transformer-based multitask network integrating CT-derived habitat and 2.5-dimensional (2.5D) deep learning features for simultaneously predicting early disease control (DC) and overall survival (OS). Of 1,234 patients with HCC enrolled from eight institutions and public databases, 832 ICI-treated patients were used for model development. ECOS-Net fused features using multi-head attention and generated early DC probabilities and OS risk scores. ECOS-DC achieved AUCs of 0.836, 0.822, and 0.817 in training, internal validation, and external test sets, outperforming clinical models (all p values < 0.05). ECOS-OS yielded C-indices of 0.730, 0.722, and 0.720, respectively. Integrated models also showed favorable external performance (early DC AUC: 0.825; OS C-index: 0.741). Patients with higher ECOS-DC probabilities had a higher likelihood of early DC, whereas those with higher ECOS-OS risk had shorter OS, with directionally consistent associations across most subgroups. Exploratory biological analyses suggested that the higher ECOS-DC probability and lower ECOS-OS risk groups were associated with immune-active tumor microenvironment features. Therefore, ECOS-Net shows potential as a non-invasive imaging-based risk stratification framework for simultaneously predicting early DC and OS in ICI-treated HCC patients.

PMID:42801546 | PMC:PMC13616327 | DOI:10.1002/advs.78005

J Inflamm Res. 2026 Sep 22;19:606503. doi: 10.2147/JIR.S606503. eCollection 2026.

ABSTRACT

BACKGROUND: Neutrophil extracellular traps (NETs) were key factors mediating inflammatory injury in acute pancreatitis (AP). To this end, there was an urgent need to identify precise and effective therapeutic targets that modulate NETs formation, providing new ideas for the prevention and treatment of AP pancreatitis injury.

GAP: To address this gap, we investigated the potential involvement of the myo-inositol metabolism in modulating NETs and inflammatory damage during AP.

METHODS: Multi-omics analysis identified myo-inositol metabolism as critical. We then established the in vitro NETs model using phorbol-12-myristate-13-acetate (PMA) to investigate the role and regulatory mechanism of inositol-3-phosphate synthase 1 (ISYNA1) on NETs formation. Finally, the findings were validated in the classic AP mouse model to verify the correlation between myo-inositol metabolism and AP pathogenesis.

RESULTS: Multiple omics analyses showed that the myo-inositol metabolic pathway is the most significant, and the key enzyme ISYNA1 involved in myo-inositol synthesis was significantly reduced. ISYNA1 was significantly downregulated in both the in vitro NETs model and in neutrophils infiltrating the pancreatic tissue of AP mice. Meanwhile, exogenous supplementation of ISYNA1 or myo-inositol significantly inhibited the NETs formation in vitro and inflammatory injury in AP mice. Mechanistically, downregulation of ISYNA1 led to reduced myo-inositol synthesis, thereby promoting NETs formation via modulation of the PI3K/AKT pathway.

CONCLUSION: ISYNA1 and myo-inositol metabolism were among the key links that regulated NETs formation and inflammatory injury in AP. Therefore, enhancing ISYNA1 and myo-inositol metabolism might serve as a potential intervention target for treating acute organ injury in AP.

PMID:42801157 | PMC:PMC13615823 | DOI:10.2147/JIR.S606503

Crit Rev Oncol Hematol. 2026 Mar 27;222:105305. doi: 10.1016/j.critrevonc.2026.105305. Online ahead of print.

ABSTRACT

The management of hepatocellular carcinoma (HCC) faces substantial and evolving challenges, driven by its aggressive biology, drug resistance, and the clinical urgency to detect recurrence. The treatment paradigm has undergone a profound transformation, evolving from surgical interventions and molecular targeted agents to the current era dominated by immunotherapy. Immune checkpoint inhibitors, particularly when used in combination with anti-angiogenic drugs or as part of dual-checkpoint blockade regimens, have established a new first-line standard of treatment for advanced HCC, delivering unprecedented survival improvements. Despite this progress, significant obstacles remain, including primary and acquired resistance, variable patient responses, and notably reduced efficacy in specific etiological subgroups. This comprehensive review synthesizes the emerging modalities such as bispecific antibodies, adoptive cell therapies, and innovative rational combinations that integrate systemic immunotherapy with locoregional treatments or novel targeted agents. Furthermore, we delve into the critical search for predictive biomarkers, encompassing liquid biopsy and multi-omics approaches, and dissect the complex cellular and molecular mechanisms underlying therapeutic resistance within the immunosuppressive tumor microenvironment. Finally, we outline future translational directions, emphasizing the expansion of immunotherapy, the development of tailored strategies for therapy-resistant disease, and the imperative move towards a personalized, biomarker-driven treatment framework. This review provides a cohesive overview of the field and charts a roadmap for future research to overcome the current challenges in HCC immunotherapy.

PMID:41905572 | DOI:10.1016/j.critrevonc.2026.105305

J Cancer. 2026 Jan 30;17(3):515-523. doi: 10.7150/jca.127381. eCollection 2026.

ABSTRACT

Gastrointestinal (GI) cancers remain a leading cause of cancer-related morbidity and mortality worldwide, largely due to their molecular heterogeneity, complex tumor microenvironment (TME), and variable treatment responses. In recent years, the emergence of spatially resolved omics technologies-encompassing spatial transcriptomics, proteomics, metabolomics, and epigenomics-has revolutionized the ability to interrogate tumor architecture with unprecedented resolution. These methods enable precise mapping of cellular and molecular interactions within intact tissue contexts, thereby uncovering spatially defined niches that influence tumor progression, immune evasion, and therapeutic resistance. In GI malignancies such as colorectal, gastric, and esophageal cancers, spatial omics have provided critical insights into cancer-stromal-immune crosstalk, identified predictive biomarkers for immunotherapy and targeted agents, and guided the development of novel therapeutic strategies. This review synthesizes the latest advances in spatial omics applied to GI oncology over the past five years, with an emphasis on their integration into early diagnosis, treatment stratification, and real-time monitoring of therapeutic efficacy. We also discuss current challenges, including standardization, data integration, and clinical validation, as well as future directions for incorporating spatial profiling into routine oncology practice. By bridging the gap between bench discoveries and bedside applications, spatial omics hold transformative potential for achieving truly personalized treatment in gastrointestinal cancers.

PMID:41869445 | PMC:PMC13003551 | DOI:10.7150/jca.127381

Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.

ABSTRACT

BACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.

METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was applied to define lactate-associated molecular subtypes, followed by characterization of survival and tumor microenvironment features. A LASSO-based gene signature was developed to generate an individual-level risk score and an integrated nomogram. Multi-omics analyses were used to evaluate concordance between transcriptomic and proteomic alterations. Single-cell transcriptomic data were analyzed to explore cellular heterogeneity in lactate-related programs. In vitro assays evaluated the response of candidate genes to lactate exposure and assessed cell migration and invasion under proliferation-inhibited conditions after genetic perturbation.

RESULTS: Two lactate-associated molecular subtypes were identified with distinct overall survival and divergent immune microenvironment features. Subtype 1 was associated with better outcomes and a more immune-inflamed profile, whereas Subtype 2 was associated with poorer outcomes and a myeloid-enriched, immunosuppressive contexture. Pathway analyses indicated subtype-associated differences in extracellular matrix-related processes and apoptosis-associated signaling. We developed an 11-gene prognostic signature and nomogram that stratified patients by risk across TCGA and GEO cohorts. Multi-omics integration highlighted ANLN, FGA, and DKK1 as consistently dysregulated at both transcript and protein levels. Among these candidates, DKK1 showed lactate-responsive induction in vitro. DKK1 perturbation altered lactate-enhanced migratory and invasive phenotypes and was accompanied by changes in intracellular lactate levels and global protein lactylation, supporting a potential feedforward relationship between lactate exposure, DKK1 expression, and lactylation.

CONCLUSIONS: This study characterizes lactate-associated molecular heterogeneity in lung cancer and provides a lactate-related subtype framework and prognostic risk model for patient stratification. The findings nominate DKK1 as a lactate-responsive candidate linked to migration/invasion phenotypes and lactate/lactylation changes in vitro.

PMID:41827671 | PMC:PMC12985219 | DOI:10.3390/cancers18050735

Cancers (Basel). 2026 Feb 25;18(5):735. doi: 10.3390/cancers18050735.

ABSTRACT

BACKGROUND: Lactate accumulation is increasingly recognized as a feature of tumor metabolic reprogramming that can coincide with immune dysregulation and aggressive phenotypes. The prognostic and immunologic relevance of lactate-associated heterogeneity in lung cancer remains to be clarified.

METHODS: We curated lactate-related genes and identified prognostic candidates in lung cancer cohorts. Consensus clustering was applied to define lactate-associated molecular subtypes, followed by characterization of survival and tumor microenvironment features. A LASSO-based gene signature was developed to generate an individual-level risk score and an integrated nomogram. Multi-omics analyses were used to evaluate concordance between transcriptomic and proteomic alterations. Single-cell transcriptomic data were analyzed to explore cellular heterogeneity in lactate-related programs. In vitro assays evaluated the response of candidate genes to lactate exposure and assessed cell migration and invasion under proliferation-inhibited conditions after genetic perturbation.

RESULTS: Two lactate-associated molecular subtypes were identified with distinct overall survival and divergent immune microenvironment features. Subtype 1 was associated with better outcomes and a more immune-inflamed profile, whereas Subtype 2 was associated with poorer outcomes and a myeloid-enriched, immunosuppressive contexture. Pathway analyses indicated subtype-associated differences in extracellular matrix-related processes and apoptosis-associated signaling. We developed an 11-gene prognostic signature and nomogram that stratified patients by risk across TCGA and GEO cohorts. Multi-omics integration highlighted ANLN, FGA, and DKK1 as consistently dysregulated at both transcript and protein levels. Among these candidates, DKK1 showed lactate-responsive induction in vitro. DKK1 perturbation altered lactate-enhanced migratory and invasive phenotypes and was accompanied by changes in intracellular lactate levels and global protein lactylation, supporting a potential feedforward relationship between lactate exposure, DKK1 expression, and lactylation.

CONCLUSIONS: This study characterizes lactate-associated molecular heterogeneity in lung cancer and provides a lactate-related subtype framework and prognostic risk model for patient stratification. The findings nominate DKK1 as a lactate-responsive candidate linked to migration/invasion phenotypes and lactate/lactylation changes in vitro.

PMID:41827671 | PMC:PMC12985219 | DOI:10.3390/cancers18050735