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Results for “Biomarker stratification”

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PubMed2005

Inflammatory biomarkers of coronary atheromatous plaque vulnerability.

In the last decade, compelling evidence has evolved at both the basic science and clinical level for the implication of inflammation in the pathogenesis of atherosclerosis and its complications. The composition of the atherosclerotic plaque, rather than the degree of stenosis, is now recognized as a pivotal feature in determining plaque vulnerability and hence the risk of acute coronary ischaemic events. Current evidence supports a key role for inflammation in all phases of the atherosclerotic process, from plaque formation through to progression and, ultimately, the thrombotic complications of atherosclerosis. The growing appreciation of the role of inflammation in atherogenesis has focused attention on whether circulating levels of inflammatory biomarkers may help to identify those at risk of future cardiovascular events. In addition, the protective effects of a variety of interventions, such as statins, aspirin, and fibrates, are often associated with the evidence of reduced inflammation, further strengthening the notion that inflammation and the acute complications of atherosclerosis are causally related. The present review describes the pathophysiology of atheromatous plaque vulnerability and discusses the clinical use of inflammatory biomarkers for prognostic stratification of patients with acute coronary syndromes.

Biomarkers↗

PubMed2006

Cardiovascular biomarkers in CKD: pathophysiology and implications for clinical management of cardiac disease.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with all forms of chronic kidney disease (CKD). The underlying pathological state is caused by a complex interplay of traditional and nontraditional risk factors that results in atherosclerosis, arteriosclerosis, and altered cardiac morphological characteristics. This multifactorial disease introduces new challenges in predicting and treating patients with CVD sufficiently early in the course of CKD to positively alter patient outcome. Asymptomatic individuals with progressive CVD are a group of patients that deserve focused attention because early detection and intervention may provide the best opportunity for improved outcome. However, identifying CVD in asymptomatic patients with CKD or end-stage renal disease remains a significant hurdle in the management of these patients. Recently, a number of cardiovascular biomarkers were identified as predictors of patient outcome in individuals with CVD and, with additional research, may be used to guide the early diagnosis of and therapy for CVD in patients with CKD. This review examines the pathophysiological characteristics and potential clinical role of these novel cardiovascular biomarkers in risk stratification, risk monitoring, and selection of preventive therapies for patients with CKD.

Biomarkers↗

PubMed2003

Natriuretic peptide hormone measurement in acute coronary syndromes.

Cardiac Ischemia is an important trigger for the release of B-type natriuretic peptide (BNP). BNP and N-terminal pro-BNP (N-proBNP) are emerging as important biomarkers for risk stratification in patients with acute coronary syndromes. Higher levels of BNP and pro-BNP are associated with a greater risk for death and heart failure, independent of traditional clinical variables and levels of other biomarkers such as troponins and C-reactive protein. The therapeutic implications of these findings are not yet known.

Acute Disease↗

PubMed2026

The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.

The ECM is a dynamic component of the tumor microenvironment with a critical role in cancer progression, invasion, metastasis, immune exclusion, and response to therapy. Recent advances in proteomic analyses investigating the insoluble ECM fractions (termed "matrisome analysis"), along with single-cell RNA sequencing and spatial transcriptomics, have revealed cancer-specific patterns of ECM remodeling. These studies have identified a panel of recurrently upregulated ECM proteins, including annexin A1, fibrillin-1, fibronectin, periostin, and tenascin-C, actively contributing to tumor growth, invasion, angiogenesis, and immune exclusion. The expression of the cancer-associated ECM is largely driven by cancer-associated fibroblasts (CAFs), whose molecular diversity has been dissected through single-cell profiling and consolidated in emerging CAF atlases across cancers. By investigating the matrisome composition and CAF heterogeneity, these studies have unraveled the pivotal role of the stroma in shaping tumor biology. Based on these discoveries, ECM proteins and CAFs are now being explored as biomarkers and therapeutic targets. Future integration of multi-omics datasets with clinical outcomes will help to translate these insights into novel biomarkers for patient stratification and stroma-directed therapeutic interventions.

Humans↗

PubMed2023

Immunogenomics of cholangiocarcinoma.

The development of cholangiocarcinoma spans years, if not decades, during which the immune system becomes corrupted and permissive to primary tumor development and metastasis. This involves subversion of local immunity at tumor sites, as well as systemic immunity and the wider host response. While immune dysfunction is a hallmark of all cholangiocarcinoma, the specific steps of the cancer-immunity cycle that are perturbed differ between patients. Heterogeneous immune functionality impacts the evolutionary development, pathobiological behavior, and therapeutic response of these tumors. Integrative genomic analyses of thousands of primary tumors have supported a biological rationale for immune-based stratification of patients, encompassing immune cell composition and functionality. However, discerning immune alterations responsible for promoting tumor initiation, maintenance, and progression from those present as bystander events remains challenging. Functionally uncoupling the tumor-promoting or tumor-suppressing roles of immune profiles will be critical for identifying new immunomodulatory treatment strategies and associated biomarkers for patient stratification. This review will discuss the immunogenomics of cholangiocarcinoma, including the impact of genomic alterations on immune functionality, subversion of the cancer-immunity cycle, as well as clinical implications for existing and novel treatment strategies.

Humans↗

PubMed2026

Systemic treatment of advanced pancreatic cancer: A Comprehensive Review.

IMPORTANCE: Pancreatic adenocarcinoma (PDAC) is an uncommon but potentially catastrophic diagnosis with historically poor prognosis. It is the tenth most prevalent cancer in the US & UK. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, with a five-year survival rate of approximately 10%. Despite increasing understanding of its molecular biology, systemic treatment options for advanced disease remain limited, and survival outcomes have improved only modestly over the past decade. OBSERVATIONS: This narrative review traces the evolution of systemic therapy for advanced PDAC from gemcitabine monotherapy through the landmark FOLFIRINOX (PRODIGE trial) and gemcitabine/nab-paclitaxel (MPACT trial) combination regimens, which remain the standard of care. Second-line options including liposomal irinotecan plus 5-FU/LV (NAPOLI-1) and maintenance olaparib for germline BRCA1/2-mutated disease (POLO) are also reviewed. Emerging data on sequential treatment strategies (SEQUENCE trial), biomarker-driven treatment selection (PRIMUS-001, PASS-01), and precision medicine approaches targeting actionable molecular subgroups, including dMMR/MSI-H, NTRK fusions, and homologous recombination deficiency are discussed. Real-world evidence comparing FOLFIRINOX and gemcitabine/nab-paclitaxel is critically appraised, including the challenges of patient selection, tolerance, and applicability outside clinical trial settings. CONCLUSION AND RELEVANCE: Despite incremental progress, the treatment landscape of advanced PDAC remains challenging. Molecular stratification and biomarker-driven precision oncology represent the most promising path forward. This review serves as a clinical reference for physicians managing advanced pancreatic cancer, highlighting current evidence, evidence limitations, and future research priorities including prospective biomarker-driven trials and improved access to genomic testing.

Biomarkers↗

PubMed2024

Proteomic Heterogeneity of the Extracellular Matrix Identifies Histologic Subtype-Specific Fibroblast in Gastric Cancer.

Gastric cancer (GC) is a highly heterogeneous disease regarding histologic features, genotypes, and molecular phenotypes. Here, we investigate extracellular matrix (ECM)-centric analysis, examining its association with histologic subtypes and patient prognosis in human GC. We performed quantitative proteomic analysis of decellularized GC tissues that characterizes tumorous ECM, highlighting proteomic heterogeneity in ECM components. We identified 20 tumor-enriched proteins including four glycoproteins, serpin family H member 1 (SERPINH1), annexin family (ANXA3/4/5/13), S100A family (S100A6/8/9), MMP14, and other matrisome-associated proteins. In addition, histopathological characteristics of GC reveals differential expression in ECM composition, with the poorly cohesive carcinoma-not otherwise specified (PCC-NOS) subtype being distinctly demarcated from other histologic subtypes. Integrating ECM proteomics with single-cell RNA sequencing, we identified crucial molecular markers in the PCC-NOS-specific stroma. PCC-NOS-enriched matrisome proteins and gene expression signatures of adipogenic cancer-associated fibroblasts (CAFadi) are closely linked, both associated with adverse outcomes in GC. Using tumor microarray analysis, we confirmed the CAFadi surface marker, ATP binding cassette subfamily A member 8 (ABCA8), predominantly present in PCC-NOS tumors. Our ECM-focused analysis paves the way for studies to determine their utility as biomarkers for patient stratification, offering valuable insights for linking molecular and histologic features in GC.

Humans↗

PubMed2025

Ferroptosis in Oral Cancer: Mechanistic Insights and Clinical Prospects.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal vulnerability in oral squamous cell carcinoma (OSCC). This review provides an overview of ferroptosis mechanisms and their implications for OSCC pathobiology and therapy. OSCC cells exhibit heightened reliance on anti-ferroptotic defenses such as GPX4, SLC7A11, FSP1, and Nrf2, and disrupting these pathways suppresses tumor growth and restores sensitivity to chemotherapy, radiotherapy, and immunotherapy. Genetic and epigenetic regulators, including p53, PER1, circ_0000140, and STARD4-AS1, critically modulate ferroptotic sensitivity, while metabolic enzymes such as ACSL4, LPCAT3, and TPI1 link ferroptosis to cellular plasticity and resistance. Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. We further address ferroptosis within the tumor microenvironment, highlighting its immunogenic and context-dependent dual roles, and summarize genomic and transcriptomic evidence linking ferroptosis-related genes to patient prognosis. Beyond cancer, ferroptosis also contributes to non-malignant oral diseases, including pulpitis, periodontitis, and infection-associated inflammation, where inhibitors may protect tissues. Despite these advances, clinical translation is constrained by the lack of safe ferroptosis inducers and validated biomarkers. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management.

Humans↗

PubMed2026

An Integrated Machine Learning and Genomic Framework for Precise Detection of Gastric Cancer.

This study presents a novel integrative approach for the analysis of high-dimensional gene expression data, leveraging the complementary strengths of unsupervised clustering and supervised classification. Using K-means clustering, the data set is stratified into three distinct clusters, revealing intrinsic biological patterns and relationships. The resulting cluster assignments are subsequently used as pseudolabels to train machine learning models, including support vector machines, random forest, and a stacking ensemble classifier. To validate and enhance the robustness of clustering, complementary methods, such as hierarchical clustering and density-based spatial clustering of applications with noise (DBSCAN), are used, with results visualized through principal component analysis-driven dimensionality reduction. The high predictive accuracy achieved by the classifiers underlines the separability and reliability of the identified clusters. Furthermore, feature importance analysis highlighted key genetic determinants within each cluster, offering actionable insights into potential biomarkers and critical genomic features. This framework bridges the gap between exploratory unsupervised learning and predictive supervised modeling, providing a scalable and interpretable method for analyzing complex genomic data sets. Its applicability extends to biomarker discovery, patient stratification, and other precision medicine applications, emphasizing its utility in advancing genomic research and clinical practice.

Humans↗

PubMed2026

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Humans↗

PubMed2026

Intratumoral PD-1+LAG-3+CD8+ T cells are associated with improved prognosis in gastric cancer.

PURPOSE: PD-1 and LAG-3 are frequently used as markers of T cell exhaustion, yet the prognostic relevance and phenotypic characteristics of PD-1+LAG-3+CD8+ T cells in gastric cancer (GC) remain poorly defined. This study aimed to investigate their association with clinical outcomes and characterize their immune characteristics across independent GC cohorts. METHODS: Four independent GC cohorts were analyzed: the Zhongshan Hospital cohort (ZSGC, n = 298), The Cancer Genome Atlas cohort (TCGA, n = 371), an Immune Checkpoint Blockade cohort (ICB, n = 45), and the Yonsei cohort (n = 433). Intratumoral PD-1+LAG-3+CD8+ T cell infiltration was quantified by immunofluorescence staining and transcriptomic gene signature scoring. Survival analysis was performed using Kaplan-Meier estimation and multivariate Cox regression. Functional characterization was performed by flow cytometry on resected GC tissue. The immune microenvironment composition was evaluated using computational analyses. RESULTS: PD-1+LAG-3+CD8+ T cells were enriched within tumors compared to adjacent normal mucosa, and their infiltration correlated with advanced tumor stage, poor differentiation, microsatellite instability, and Epstein-Barr virus (EBV)-positive molecular subtypes. High intratumoral infiltration was significantly associated with improved overall survival in both the ZSGC and TCGA cohorts, whereas single-positive PD-1+CD8+ or LAG-3+CD8+ T cells showed no such association. In the ICB cohort, higher infiltration was associated with a higher response rate to pembrolizumab. Intratumoral PD-1+LAG-3+CD8+ T cells exhibit an activated phenotype characterized by increased expression of CD137, IFN-γ, perforin, and CXCL13, along with elevated TCF7 and lower PD-1 levels, suggesting a tumor-reactive, pre-exhausted state. High infiltration was further associated with an immune-active tumor microenvironment. CONCLUSIONS: High intratumoral infiltration of PD-1+LAG-3+CD8+ T cells is associated with favorable prognosis and an immune-active microenvironment in GC. These cells display phenotypic features consistent with a pre-exhausted state and may serve as independent prognostic biomarkers and candidate predictive biomarkers for immunotherapy stratification.

Humans↗

PubMed2026

Evaluation of the clinical and mechanistic role of MCM2 expression in the prediction of meningioma recurrence after radiotherapy.

OBJECTIVE: Postoperative radiotherapy is an effective treatment for meningiomas; however, treatment response varies among patients. In addition, practical methods for predicting tumor recurrence after radiotherapy have not been well established. Minichromosome maintenance protein 2 (MCM2), a key regulator of DNA replication licensing, was recently implicated in highly proliferative molecular subtypes of meningioma. In this study, the authors evaluated whether MCM2 immunohistochemical expression predicts response to radiotherapy in patients with meningiomas. METHODS: The authors retrospectively analyzed the records of patients with WHO grade 1-3 meningiomas treated with resection followed by radiotherapy at a single institution between July 2003 and November 2023. The MCM2 labeling index was assessed immunohistochemically, and patients were stratified into MCM2-high and -low groups using a cutoff of 35%. Progression-free survival (PFS) was defined as the interval from the completion of radiation therapy to postoperative radiological tumor recurrence or regrowth. Patients who showed no progression were censored at their last follow-up. PFS was estimated using Kaplan-Meier analysis and subsequently evaluated with Cox proportional hazards models. To further investigate the biological mechanisms associated with MCM2 expression, comprehensive transcriptomic analyses, including gene set enrichment analysis, was performed to elucidate the molecular processes that occur within MCM2-high tumors. RESULTS: The study population included 15 men (42%) and 21 women (58%), with a mean age of 63 years. Ten tumors (28%) were classified as MCM2-high meningiomas and 26 (72%) as MCM2-low meningiomas. High MCM2 expression was significantly associated with WHO grades 2-3 histology and higher Ki-67 labeling indices. During a median follow-up of 2.52 years, tumor progression after radiotherapy occurred in 47% of the patients. High MCM2 expression (HR 8.34, p = 0.03) was significantly associated with shorter PFS and remained an independent predictor of recurrence after adjustment for WHO grade, tumor size, and Ki-67 labeling index. Transcriptomic analyses of MCM2-high tumors revealed upregulation of cell proliferation-related pathways, accompanied by increased signaling through the E2F8-CHEK1 axis associated with radiation resistance and suppression of the TNF-α signaling pathway implicated in radiosensitivity. CONCLUSIONS: In meningiomas, high MCM2 expression is associated with early recurrence following radiotherapy. The study findings suggest that this association is driven by diverse biological mechanisms related to cell cycle regulation and radioresistance. Immunohistochemical assessment of MCM2 expression may serve as a practical and accessible biomarker for risk stratification and may support the future development of individualized postoperative radiotherapy strategies.

Humans↗

PubMed2026

Prognostic value of circulating tumor DNA and copy-number alterations in patients receiving tandem [225Ac]Ac-/[177Lu]Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer: a prospective observational study.

BACKGROUND: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) demonstrates clinical efficacy in metastatic castration-resistant prostate cancer (mCRPC), yet robust biomarkers for dynamic treatment monitoring and resistance remain lacking. We investigated circulating tumor DNA (ctDNA)-derived tumor fraction (TFx) and genome-wide copy-number alterations (CNAs) as non-invasive biomarkers of treatment response and resistance biology. METHODS: Seventy-eight patients with advanced mCRPC receiving tandem [225Ac]Ac-/[177Lu]Lu-PSMA-617 were prospectively enrolled. Plasma samples collected longitudinally (n = 172) underwent ultra-low-pass whole-genome sequencing. TFx was estimated using ichorCNA, and recurrent CNAs were identified using GISTIC2.0. Associations with progression and overall survival (OS) were assessed using Cox proportional hazards models, including time-dependent analyses. RESULTS: Baseline TFx differed across metastatic disease stages (p = 0.027) and dynamic TFx changes paralleled PSA kinetics during early treatment. Modelled as a time-dependent variable, TFx was associated with a significantly increased risk of progression (HR 4.9, 95% CI 1.2-20.1, p = 0.026). Unsupervised clustering identified distinct high- and low-CNA burden groups strongly correlated with TFx (p = 8.09 × 10⁻8). High CNA burden was associated with shorter median OS (8.3 vs 13.8 months). Multivariable analysis identified baseline logPSA and logALP as independent predictors of OS. Recurrent CNAs affected key tumor suppressors (PTEN, RB1, BRCA2, ATM) and were enriched in pathways related to TP53 signalling, homologous recombination repair, and oncogenic signaling. Longitudinal analyses demonstrated persistence and expansion of specific amplifications at progression. CONCLUSIONS: ctDNA-derived TFx represents a dynamic biomarker of treatment response and progression risk, while CNA profiling provides insight into resistance mechanisms in mCRPC treated with PSMA-RLT. These findings support the integration of ctDNA-based biomarkers into clinical stratification and real-time monitoring strategies.

Humans↗

PubMed2026

Tumor-Infiltrating Clonal Hematopoiesis Is Associated with Adverse Clinical Outcomes in Diffuse Large B-cell Lymphoma.

UNLABELLED: Tumor-infiltrating clonal hematopoiesis (TI-CH) contributes to the progression of nonhematologic cancers. CH is prevalent in the peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), but TI-CH prevalence and clinical relevance remain largely unexplored. In this study, through genome- and exome-wide sequencing of DLBCL biopsies and blood samples from 304 treatment-naïve patients, we identified TI-CH in 13.5% of cases, which emerged as an independent risk indicator for disease progression and death. TI-CH cases had an enrichment of inflammatory myeloid signatures revealed by gene expression profiling of tumor biopsies. In addition, we developed a TI-CH-associated prognostic signature (CAPS) based on 24 differentially expressed genes. A high CAPS score correlated with poor survival across four patient cohorts and remained significant in three cohorts after adjustment for patient age, sex, International Prognostic Index score, and cell-of-origin classification. Collectively, these findings establish a link between TI-CH and clinical outcomes and implicate the inflammatory signature as the potential underlying basis. SIGNIFICANCE: TI-CH correlates with disease progression and death in patients and with the inflammatory modeling of the DLBCL tumor microenvironment. Our results underscore the clinical and biological relevance of TI-CH and suggest its potential as a biomarker for risk stratification and as a target for therapeutic intervention in DLBCL.

Humans↗

PubMed2023

International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance.

Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i.e. increased early tumour detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts. To address these issues, ILCA (the International Liver Cancer Association) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies.

Humans↗

PubMed2026

Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.

Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8+T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.

Humans↗

PubMed2006

[Diagnosis and therapy of pulmonary embolism].

Management of venous thromboembolism has long been characterized by a high degree of complexity and a disappointing lack of both efficacy and efficiency. The non-specific clinical signs of acute pulmonary embolism (PE) and the limitations of earlier imaging procedures such as the lung scan and pulmonary angiography led to the development of numerous sophisticated, multi-step diagnostic algorithms which, however, have proved extremely difficult to implement in clinical practice. As a result, the diagnosis of potentially life-threatening PE was frequently missed in many patients who subsequently died of the disease without receiving appropriate treatment, while other patients unnecessarily underwent a battery of invasive, time consuming procedures due to a vague, poorly documented clinical suspicion. Recently, the development of structured models for assessment of clinical pre-test probability, the widespread use of D-dimer testing in the outpatient setting, and particularly the technical advances of multidetector-row CT scan, had an enormous impact on our strategy for approaching patients with suspected PE. Contemporary diagnostic algorithms based on the above modalities are not only efficient and reliable but also simple and practicable. Furthermore, the importance of right ventricular (RV) dysfunction, even in the absence of overt hemodynamic instability, was recognized, and a number of studies demonstrated the value of echocardiography and laboratory biomarkers for risk stratification of PE. At present, low molecular weight heparins are increasingly becoming established as the treatment of choice for hemodynamically stable patients without RV dysfunction (non-massive PE), while consensus exists that patients with massive PE and cardiogenic shock necessitate emergency removal of pulmonary thrombus using thrombolytic agents, surgical embolectomy, or catheter-based thrombus aspiration. On the other hand, the treatment of stable patients with RV dysfunction (submassive PE) remains the subject of debate, and a large randomized trial is urgently needed to address the possible clinical benefits of thrombolysis in this setting.

Algorithms↗

PubMed2026

Amplification-Driven S100A11 Overexpression in Hepatocellular Carcinoma Is Associated with Metabolic Reprogramming, ECM Remodelling, and Immune Evasion: A Pan-Cancer Genomic Study.

BACKGROUND: S100A11, a calcium-binding S100 family protein, is increasingly implicated in carcinogenesis, yet its molecular regulation and clinical relevance across cancers remain unclear. Hepatocellular carcinoma (HCC) carries a dismal prognosis, in part due to a lack of reliable biomarkers for risk stratification of established disease. METHODS: We conducted a pan-cancer analysis of S100A11 genomic alterations across 31 studies (10,767 samples) obtained from TCGA, encompassing copy number alterations, somatic mutations, and DNA methylation. HCC-specific analyses evaluated S100A11 expression, its potential as a diagnostic/prognostic marker, co-expression networks, and pathway enrichment using TCGA-LIHC data, with univariate and multivariate Cox regression to assess survival associations. RESULTS: S100A11 alterations were predominantly driven by copy number amplification, with the highest frequencies in hepatobiliary cancers, lung and breast cancers. Copy number amplification showed a consistent inverse relationship with promoter methylation, indicating amplification-driven transcriptional activation. In HCC, S100A11 was markedly overexpressed compared with normal liver tissue, with strong diagnostic discriminatory capacity. High S100A11 expression was significantly associated with inferior overall survival (log-rank p = 0.032; HR = 1.46, 95% CI 1.03-2.06) and remained an independent predictor of overall survival after adjustment for age, sex, and AJCC pathologic stage (HR = 1.27, 95% CI 1.01-1.60, p = 0.038). Co-expression and pathway analyses demonstrated an association between S100A11 and metabolic reprogramming, extracellular matrix remodelling, and immune dysregulation. CONCLUSIONS: These findings identify S100A11 as a candidate diagnostic and prognostic biomarker in HCC whose overexpression is associated with metabolic reprogramming, ECM remodelling, and immune dysregulation, warranting experimental validation of a mechanistic role.

ECM↗