INTRODUCTION: Pancreatic cancer (PC) has an insidious onset, limited treatment, and a poor prognosis. Extracellular vesicles (EVs) play a crucial role as a bridge for tumor microenvironment (TME)communication in tumorige...INTRODUCTION: Pancreatic cancer (PC) has an insidious onset, limited treatment, and a poor prognosis. Extracellular vesicles (EVs) play a crucial role as a bridge for tumor microenvironment (TME)communication in tumorigenesis and development, especially EV proteins reflect the specificity of tumors. EVs serve as readily available biomarkers, and characterization of their protein profiles is expected to be a noninvasive molecular marker to improve the early diagnosis of Pancreatic ductal adenocarcinoma (PDAC) as well as potential therapeutic targets. AREAS COVERED: This review focuses on the mechanism by which all types of EV proteins are involved in PDAC. In addition, this review summarizes EV proteins as potential targets for the diagnosis and treatment of PDAC to fully understand the promise of EV proteins as liquid biopsies for PDAC. EXPERT OPINION: EVs in the humoral circulation represent an important part of liquid biopsy detection. EV protein profiling can be used as a liquid biopsy tool to detect cancer and distinguish cancer types. EV proteins have the characteristics of high specificity and sensitivity, but in view of the heterogeneity of tumors, EVs can be used as effective carriers for multiple candidate marker panels, and gradually realize personalized medicine for automated detection in the future.
Goli M, Gutierrez-Reyes CD, Sandilya V
… +10 more, Sahioun S, Oluokun A, Oluokun O, Purba W, Chukwubueze F, Bhuiyan MMAA, Mondello S, Wang KK, Kobeissy F, Mechref Y
INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with current diagnostic tools often inadequate for predicting long-term outcomes. Omics studies have identified specific bi...INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with current diagnostic tools often inadequate for predicting long-term outcomes. Omics studies have identified specific biomarkers for TBI, and recently, glycoproteins have emerged as promising novel biomarkers due to their pivotal roles in cellular signaling and structural integrity. AREAS COVERED: This review explores the biological significance of glycoproteins in TBI, their altered glycosylation patterns post-injury, and their role as diagnostic and prognostic indicators. We summarize analytical techniques for glycoprotein detection, such as mass spectrometry and antibody-based assays. Key glycoproteins, including neurofilament proteins, GFAP, tau, and amyloid precursor proteins, are examined for clinical relevance. This review addresses challenges in glycoprotein biomarker research, like glycosylation complexity and the need for precise detection methods. EXPERT OPINION: Clinical research from our lab and others have underscored the role of glycoproteins in diagnosing TBI, assessing injury severity, and guiding therapeutic strategies. By addressing the current state and future directions of glycoprotein research, we aim to potentially highlight the path toward improved diagnostic and therapeutic approaches for TBI.
INTRODUCTION: The introduction of biomarkers in precision medicine is heralding a new era of diagnostic power and personalized patient care. Biomarkers are critical tools for detecting various diseases, guiding treatment...INTRODUCTION: The introduction of biomarkers in precision medicine is heralding a new era of diagnostic power and personalized patient care. Biomarkers are critical tools for detecting various diseases, guiding treatment decisions, and predicting patient responses, thereby improving outcomes and reducing healthcare costs. AREAS COVERED: This review examines the regulatory landscape governing biomarker development and utility, focusing on major frameworks established by well-known regulatory agencies. A broad literature review demonstrates how these frameworks extend from research to clinical application. Also, the review article presents the challenges in biomarker translation and valuable recommendations for overcoming these barriers, while it discusses the future trends in biomarker regulation, including the impact of artificial intelligence (AI) and multi-omics approaches in identification and validation of biomarkers. EXPERT OPINION: One can conclude that future biomarker regulation will employ an adaptive regulatory framework, AI interventions, and high-throughput approaches. These innovations can transform clinical practices and improve patients' life. However, careful regulation, rigorous validation, overcoming technical - ethical challenges and the tightening quality controls of the routine labs remain essential for successful implementation in clinical practice. More global collaboration is needed among regulatory authorities, academia, industry stakeholders and bioanalytical laboratories.
INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) have revolutionized rheumatic and inflammatory diseases therapy. Despite their efficacy, at least 30% of patients do not respond to TNFi therapy. There are five FDA-a...INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) have revolutionized rheumatic and inflammatory diseases therapy. Despite their efficacy, at least 30% of patients do not respond to TNFi therapy. There are five FDA-approved TNFis and several TNFi biosimilars, which are equivalent to their reference drugs. Although all TNFi drugs neutralize the TNF cytokine, they differ in many structural and pharmacokinetic properties. These differences may lead to varying patient responses, making one TNFi, but not another, effective for a given patient. An accurate prediction of a priori responsiveness to therapy, rather than trial and error, would therefore be of great value. Biomarkers that may guide the optimal TNFi choice are an unmet need. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of Cell-Based Assays (CBAs) for individualized TNFi therapy. Selection of TNFi can be based upon a given patient's immune cell response to the various TNFi drugs to predict their clinical outcomes to those drugs. EXPERT OPINION: CBAs allow to assess the response of multiple TNFi drugs simultaneously by measuring biomarkers that could distinguish between TNFi responders and non-responders, effectively prioritizing the TNFi of choice. This literature search focuses on biomarkers and techniques that could be used as predictive CBAs for clinical response to TNFi.
INTRODUCTION: Liquid biopsy (LB) has shifted the paradigm in cancer diagnosis and management, offering a minimally invasive and dynamic approach to understanding tumor biology. Advanced next-generation sequencing (NGS) t...INTRODUCTION: Liquid biopsy (LB) has shifted the paradigm in cancer diagnosis and management, offering a minimally invasive and dynamic approach to understanding tumor biology. Advanced next-generation sequencing (NGS) technologies have significantly improved the accuracy of LB results, enhancing both its analytical and clinical validity. However, tissue biopsy (TB) remains the gold standard for molecular analysis, often negatively impacting the molecular profiling of tumor patients owing to inadequate tissue samples, or lack thereof. AREAS COVERED: In this scenario, LB has become a dynamic and easily-to-handle, integrative source of nucleic acids, filling the gap in tissue sample availability for molecular profiling. Moreover, cost-effectiveness analyses have also shown that when LB is correctly applied to clinical settings, healthcare spending can be optimized, enabling an increase in quality-adjusted life years at an affordable cost. EXPERT OPINION: While LB has the potential to reduce the need for invasive TB and expedite treatment decisions, its cost-effectiveness hinges on long-term clinical outcomes and healthcare resource utilization. In this scenario, 'new era platforms' endowed with advanced liquid handling technologies could not only improve its efficiency and reduce costs but also enable higher-throughput experiments with much larger sample sizes.
BACKGROUND: Huntington's disease (HD) is a neurodegenerative condition resulting from CAG trinucleotide expansion in the . We reviewed various molecular tools for diagnosing HD and their respective validations and outlin...BACKGROUND: Huntington's disease (HD) is a neurodegenerative condition resulting from CAG trinucleotide expansion in the . We reviewed various molecular tools for diagnosing HD and their respective validations and outlined their advantages and disadvantages. METHODS: We utilized PubMed, employing Huntington's disease OR chorea AND Molecular Diagnosis OR Molecular Diagnostic Techniques as keywords. This review was submitted to the PROSPERO platform (nºCRD42021253951). The PRISMA checklist was used, and bias assessment followed the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. RESULTS: 845 articles were retrieved, 17 were selected for full-text review, and two additional articles were manually included, resulting in 19 that presented the validation method: only three studies reported the limits of detection, reproducibility, sensitivity, and specificity, which are essential for validating these techniques, given the unstable nature of CAG regions; six calculated at least one of these parameters, and 10 did none. CONCLUSION: We identified significant variability in the validation methods with only three thoroughly assessing the key validation parameters. The lack of standardized validation approaches may compromise diagnostic accuracy, impacting genetic counseling and clinical management. TPPCR coupled with capillary electrophoresis, demonstrated high accuracy, whereas gel electrophoresis-based methods exhibited lower sensitivity and specificity.
INTRODUCTION: Circulating tumor DNA (ctDNA) is a noninvasive and promising biomarker for cancer diagnosis, prognosis, and therapeutic monitoring, offering significant potential for real-time insights into tumor dynamics...INTRODUCTION: Circulating tumor DNA (ctDNA) is a noninvasive and promising biomarker for cancer diagnosis, prognosis, and therapeutic monitoring, offering significant potential for real-time insights into tumor dynamics when compared to traditional tissue-based biopsies. Phase I oncology clinical trials, which primarily focus on assessing the safety, pharmacodynamics, and early activity of novel cancer therapies, might find in the unique biological characteristics of ctDNA, a valuable biomarker to boost the efficiency of testing novel agents. AREAS COVERED: This review explores the utility of ctDNA as a biomarker in phase I trials, discussing its biological and technical features, clinical relevance, current limitations, and future potential in advancing early clinical drug development. EXPERT OPINION: Despite being an emerging field in phase I trials, ctDNA analysis has proved to be a remarkable tool for patient inclusion, optimal biological dose determination, and early response assessment. However, several challenges hinder its systematic adoption in early trials, including assay variability, biological and anatomical differences across cancer types, and, most notably, the lack of standardization. Systematic implementation of ctDNA in phase I trials could facilitate the development of robust, reproducible noninvasive biomarker models, which can then be further validated in phae II/III trials.
INTRODUCTION: Diagnosing severe pneumonia accurately is often difficult because its clinical symptoms overlap with other respiratory illnesses. Treatment of severe lower respiratory tract infection (LRTI) should start ea...INTRODUCTION: Diagnosing severe pneumonia accurately is often difficult because its clinical symptoms overlap with other respiratory illnesses. Treatment of severe lower respiratory tract infection (LRTI) should start early. Rapid identification of responsible microorganisms and appropriate, not overly broad, antibiotic therapy is required to optimize prognosis. Unfortunately, the causative pathogen is often unidentified in pneumonia patients, and conventional bacterial cultures lack sensitivity and have slow turnaround times. Multiplex PCR (mPCR) respiratory panels, which quickly detect multiple bacterial pathogens, some common respiratory viruses, and key resistance genes, have become commercially available and may help achieve these objectives. AREAS COVERED: The authors will describe the available biological and clinical data on the benefits of mPCR in severe LRTI. EXPERT OPINION: mPCR offers early pathogen and resistance detection. However, mPCR panels do not detect all bacterial pathogens and may not differentiate between colonizing and infecting organisms. Detectable resistance genes do not always indicate phenotypic resistance. It should only be used in patients with adequate lower respiratory tract (LRT) samples. Additionally, evidence on whether mPCR panels improve antimicrobial use and patient outcomes remains limited and conflicting. This review provides a thorough overview of the rationale and clinical evidence for the use of mPCR panels for the detection of viral and bacterial pathogens in pneumonia diagnosis and management, as well as future research directions. [Figure: see text].
INTRODUCTION: Despite vaccine availability, Hepatitis B Virus (HBV) remains a major global health threat, especially in areas with low vaccination coverage and poor healthcare. Around 250 million people are chronically i...INTRODUCTION: Despite vaccine availability, Hepatitis B Virus (HBV) remains a major global health threat, especially in areas with low vaccination coverage and poor healthcare. Around 250 million people are chronically infected. Achieving the World Health Organisation's (WHO) 2030 eradication goal is difficult, particularly due to diagnostic challenges in low-resource settings. While HBsAg detection is standard, low antigen levels and mutations hinder its reliability. Though molecular methods for HBV DNA offer high specificity, their cost and complexity limit use in under-resourced areas. Isothermal amplification emerges as a promising alternative, offering a more affordable, effective, and simplified approach to HBV detection, potentially improving access to timely diagnosis and care. AREAS COVERED: This review evaluates the efficacy of various isothermal techniques to give insights into their benefits and limits, guiding researchers and clinicians in selecting the most effective assays for HBV molecular diagnostics. EXPERT OPINION: Recombinase Polymerase Amplification (RPA) and Polymerase Spiral Reaction (PSR) are the most promising isothermal assays for HBV detection in field settings. RPA is faster (∼20 min), works at low temperatures (37-42 °C), and uses stable lyophilized reagents, while PSR is simple, can be clubbed with visual detection, making both ideal for a low-resource setup.
INTRODUCTION: Biliary tract cancer (BTC) comprises a group of aggressive malignancies with poor prognosis and limited therapeutic options. Next-generation sequencing (NGS) has advanced BTC management by identifying targe...INTRODUCTION: Biliary tract cancer (BTC) comprises a group of aggressive malignancies with poor prognosis and limited therapeutic options. Next-generation sequencing (NGS) has advanced BTC management by identifying targetable genomic alterations. However, routine multigene NGS testing faces clinical, logistical, and economic barriers to widespread implementation. AREAS COVERED: A multidisciplinary panel of eight experts from Germany, France, the UK, Spain, and Italy convened to explore national challenges in NGS adoption and propose a structured molecular profiling approach. Discussions addressed pre-analytical tissue handling, sequencing strategies, and access limitations. EXPERT OPINION: Despite molecular advances, NGS access varies significantly across Europe. Barriers include suboptimal tissue sampling, restricted reimbursement, infrastructure gaps, and limited bioinformatics support. The panel recommends combined DNA and RNA sequencing as the ideal approach. In settings without NGS, referral to equipped centers is advised, with single-gene assays reserved for essential targets. This algorithm is a temporary yet practical guide to inform treatment decisions under current healthcare constraints, aiming to support equitable and informed care for BTC patients.
INTRODUCTION: Cholangiocarcinoma (CCA) is an uncommon yet aggressive malignancy often diagnosed at advanced stages. Its management is challenged by significant molecular heterogeneity and limited treatment options. Advan...INTRODUCTION: Cholangiocarcinoma (CCA) is an uncommon yet aggressive malignancy often diagnosed at advanced stages. Its management is challenged by significant molecular heterogeneity and limited treatment options. Advances in next-generation sequencing (NGS) have identified actionable alterations, such as FGFR2 fusions, thereby facilitating a precision oncology approach for CCA management. AREAS COVERED: This review consolidates current evidence and expert insights on molecular profiling in CCA. It examines the histopathological subtypes and addresses diagnostic challenges associated with their diagnosis. Critical pre-analytical factors, including biopsy techniques, tissue handling, and tumor heterogeneity, are discussed in relation to their impact on molecular testing. The review also evaluates DNA-based versus RNA-based NGS methodologies, highlighting their strengths and limitations in detecting complex genomic alterations. The role of liquid biopsy as a minimally invasive tool for dynamic tumor monitoring is also explored. EXPERT OPINION: The routine integration of molecular profiling for CCA requires the best histopathological diagnosis and pre-analytical preparation practices. Diagnostic workflows should prioritize meticulous tissue handling to ensure robust molecular analyses to avoid tissue exhaustion and preserve the integrity of nucleic acids. Employing DNA plus RNA sequencing platforms, supported by molecular tumor boards, is recommended to enhance patient stratification and guide therapeutic decision-making in CCA.
Expert Rev Mol Diagn
· 2025 Aug · PMID 40482041
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INTRODUCTION: Primary open-angle glaucoma (POAG) is an optic neuropathy, characterized by progressive loss of visual field, loss of retinal ganglion cells (RGC) and optic nerve damage. The diagnosis and management of POA...INTRODUCTION: Primary open-angle glaucoma (POAG) is an optic neuropathy, characterized by progressive loss of visual field, loss of retinal ganglion cells (RGC) and optic nerve damage. The diagnosis and management of POAG involves tests such as static perimetry, tonometry and optical coherence tomography (OCT) to track progressive structural and functional changes. All these methods have limitations. Advancements in the discovery of metabolomic plasma-derived biomarkers may improve clinical outcomes, through identifying susceptible individuals, predicting disease progression, and assessing treatment efficacy in POAG. AREAS COVERED: We reviewed the current state of POAG management, identified limitations and need for biomarkers that could potentially fill the gap and current landscape of POAG plasma metabolomics, providing an overview of future potential biomarkers. EXPERT OPINION: Advances in the identification of metabolomic biomarkers can improve current clinical practices. These biomarkers can complement existing diagnostic tools, allowing for earlier detection and personalized treatment strategies. However, challenges remain, including a lack of standardization in metabolomics protocols, variability in disease progression and finally, recording treatment non-response currently also suffers from a lack of standardization toward depicting treatment outcomes. Future research should focus on standardizing procedures, increasing diversity in study populations, and conducting longitudinal studies to validate biomarkers in clinical settings.
INTRODUCTION: Renal Cell Carcinoma (RCC) is a heterogeneous disease, with distinct clinical outcomes for each subtype. Even within subtypes, outcomes differ and there is a need for novel biomarkers enabling risk stratifi...INTRODUCTION: Renal Cell Carcinoma (RCC) is a heterogeneous disease, with distinct clinical outcomes for each subtype. Even within subtypes, outcomes differ and there is a need for novel biomarkers enabling risk stratification or predicting response to targeted therapies. AREAS COVERED: Epigenetic alterations, particularly aberrant DNA methylation and microRNAs deregulation, are a biomarker source that might be evaluated in liquid biopsies. Moreover, despite the ground knowledge that RCC comprises different histological entities, most studies still focus on 'RCC' in general and do not consider different subtypes. The most promising microRNAs for ccRCC identification are miR-210-3p, miR-21-3p, and miR-155-5p, which might help accurately subtype RCC, being closer to clinical routine but still lacking validation. Besides, miR-146-a and miR-126-a are promising biomarkers to predict response to immune checkpoint inhibitors. EXPERT OPINION: Substantial developments in molecular diagnostics have been recently made, namely regarding liquid biopsies, despite the lack of biomarkers approved for clinical routine. The inclusion of dedicated Pathologists in biomarker studies remains crucial to truly achieving clinical relevance. Furthermore, combination of artificial intelligence with molecular biomarkers may foster personalized RCC management, with improved precision.
INTRODUCTION: Autism Spectrum Disorder (ASD) affects 1 in 31 children in the U.S. highlighting the urgent need for early detection and intervention. Identifying reliable early biomarkers could revolutionize ASD diagnosis...INTRODUCTION: Autism Spectrum Disorder (ASD) affects 1 in 31 children in the U.S. highlighting the urgent need for early detection and intervention. Identifying reliable early biomarkers could revolutionize ASD diagnosis and improve outcomes by enabling timely therapeutic strategies. AREAS COVERED: This review explores maternal, paternal, and environmental risk factors contributing to ASD, including immune dysregulation, metabolic conditions, toxicant exposures, and placental and amniotic factors. Biomarkers aid in identifying these factors. EXPERT OPINION: Future research in maternal health and biomarkers is crucial for predicting ASD risk and developing personalized interventions. Advances in multi-omics, imaging, epigenetics, and AI-driven analysis can improve biomarker accuracy, enabling earlier detection and targeted therapies. However, challenges such as biomarker reliability and ASD heterogeneity must be addressed through large-scale validation studies and interdisciplinary collaboration to translate these discoveries into clinical practice effectively.
INTRODUCTION: Early diagnosis is essential for a good prognosis of patients with endometrial cancer; however, there are currently no noninvasive tests available. Despite the good prognosis with early diagnosis, a signifi...INTRODUCTION: Early diagnosis is essential for a good prognosis of patients with endometrial cancer; however, there are currently no noninvasive tests available. Despite the good prognosis with early diagnosis, a significant minority of women will recur, and biomarkers are needed to stratify patients according to their risk of recurrence. CONTEXT: In recent decades, the discovery of blood biomarkers to facilitate diagnosis and improve risk stratification of EC patients has been actively pursued. AREAS COVERED: The present review is an update of candidate blood biomarkers for the diagnosis and prognosis of endometrial cancer reported in the past eight years, following an earlier review. The literature search was conducted in the PubMed database for the period between July 2016 and September 2024. This review describes studies investigating tumor markers, proteins, metabolites and miRNAs and their diagnostic and prognostic properties. The quality of the included studies is assessed and the limitations and potential for translation into clinical application are discussed. EXPERT OPINION/COMMENTARY: Individual biomarker candidates do not offer optimal diagnostic and prognostic characteristics. The use of omics for biomarker discovery is promising, but development in this area is lagging behind due to methodological issues and a lack of external validation.
INTRODUCTION: Biomarkers have transformed fungal diagnostics by enabling early detection, risk assessment and treatment monitoring. Their clinical value depends on factors e.g. sensitivity, specificity, host immune statu...INTRODUCTION: Biomarkers have transformed fungal diagnostics by enabling early detection, risk assessment and treatment monitoring. Their clinical value depends on factors e.g. sensitivity, specificity, host immune status and technical standardization. AREA COVERED: This review covers antigen- and DNA-based methods for detecting invasive fungal infections, focusing on spp., spp. and Mucorales. EXPERT OPINION: The selection of fungal biomarkers should be tailored to patient populations, clinical setting, and suspected infections. Combining biomarkers enhances diagnostic accuracy, particularly in high-risk patients. While biomarkers indicate fungal presence, they support diagnosis and guide decisions, but must be interpreted alongside clinical context and guidelines (EORTC/MSG). [Figure: see text].