Expert Review of Molecular Diagnostics最新文献

Introduction: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive.

Areas covered: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.

Expert opinion: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.

Background: Circulating tumor DNA (ctDNA) testing of plasma for ESR1 somatic variants is essential for guiding treatment decisions in hormone receptor-positive (HR  +  ) and HER2-negative (HER2-) advanced or metastatic breast cancer (MBC) patients who have progressed on frontline therapy. To ensure optimal, uniform, and reliable ESR1 testing across China, an pilot external quality assessment (EQA) scheme was established.

Methods: Aliquots of five artificial reference plasma samples containing ESR1 mutations at varying allelic frequencies were distributed to 37 laboratories for testing and reporting according to routine procedures. The genotyping accuracy and clinical reporting were evaluated against standardized criteria, and feedback was provided to the participants.

Results: The overall genotyping error rate in the EQA was 6.29%, with 91.4% of laboratories correctly identifying the ESR1 mutational status in all samples. A variety of extraction methods and analytical techniques were employed. However, reports often failed to address the risk that tumor DNA may not have been tested, and the limitations of the methodologies used by participants were insufficiently discussed.

Conclusion: The variability in genotyping accuracy and reporting standards underscores the importance of EQA and educational guidance to ensure the provision of high-quality clinical services.

Introduction: Extracellular vesicles are membranous particles released by cells in physiological and pathological conditions. Their cargo is heterogeneous since it includes different biomolecules such as nucleic acids and proteins. Oncogenic alterations affect the composition of extracellular vesicles and model their content during cancer evolution.

Areas covered: This review provides an overview of the studies focused on extracellular vesicles as source of biomarkers in hematological malignancies. A special insight into extracellular vesicles-derived biomarkers as tools for evaluating the prognosis of hematological malignancies and their response to treatment is given.

Expert opinion: Extracellular vesicles are a valuable source of biomarkers in hematological malignancies. However, the translation from the bench to the bedside is challenged by the lack of standardization of the preanalytical variables of the experimental workflow. The release of standard operating procedures and the validation of the extracellular vesicles-derived biomarkers in large cohort of patients will help in exploiting the potential of extracellular vesicles in the clinical setting.

Introduction: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization.

Areas covered: Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas).

Expert opinion: Despite certain challenges, including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.

Introduction: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition characterized by debilitating bladder pain and urinary symptoms, such as urgency and frequency. Its considerable impact on patients' quality of life is compounded by the diagnostic challenges stemming from symptom overlap with other urological disorders and insufficient standardization of diagnostic criteria.

Areas covered: This review examines various key aspects of IC/BPS, including the identification of biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) that correlate with symptom severity and underlying inflammatory processes. It discusses the importance of urinary and serum biomarkers, current challenges in clinical assessments, the variability in biomarker collection and analysis methods, and emphasizes the role of patient-reported outcomes (PROs) such as the O'Leary - Sant (ICSI/ICPI) questionnaires and the Visual Analogue Scale in capturing the patient's subjective experience and quality of life.

Expert opinion: Strengthening the integration of biomarkers with PROs is crucial for enhancing diagnostic accuracy and personalizing treatment approaches for IC/BPS patients. The review calls for future research to develop standardized protocols, which will improve patient care by facilitating a more tailored management strategy based on a comprehensive understanding of IC/BPS.

Introduction: Sepsis is a systemic immune dysregulation syndrome triggered by secondary infection in the host, with diagnosis based on the updated Phoenix criteria and characterized by multi-organ failure as its core pathological manifestation. It is a significant global health challenge due to its increasing incidence and high mortality rates. Recent advancements in biomarker research provide promising tools for improving early diagnosis and timely intervention, essential for better patient outcomes.

Areas covered: This review examines the latest developments in pediatric sepsis biomarkers, categorized by inflammation, metabolism, organ damage, and non-coding RNAs (miRNAs, LncRNAs). We discuss the advancements in each category, highlighting the integration of diverse biomarkers and advanced technologies to enhance diagnostics, personalize therapy, and improve patient stratification.

Expert opinion: Given the limited specificity and sensitivity of current markers like CRP and PCT, multicenter studies are crucial for validating new biomarkers and for developing comprehensive panel markers that combine multiple diagnostic indicators. It is also important to consider the variability in host responses to different pathogens when identifying biomarkers based on host-pathogen interactions. To advance personalized medicine, future research may prioritize the identification of specific diagnostic biomarkers for pediatric sepsis, tailored to different pathogens.