Expert Review of Molecular Diagnostics最新文献

Introduction: In this special report, we summarize studies of cerebrospinal fluid and plasma/serum biomarker neurofilament light chain (NfL) concentrations, a key structural component of myelinated axons in neuroinfections.

Areas covered: The following infections were searched for in PubMed; Neuroinfection and biomarkers, herpes simplex encephalitis and neurofilament light chain, tick-borne encephalitis and neurofilament light chain, Lyme neuroborreliosis and neurofilament light chain, bacterial meningitis and neurofilament light chain, malaria and neurofilament light chain, COVID-19 and neurofilament light chain, HIV infection and neurofilament light chain.

Expert opinion: NfL can serve as a valuable biomarker for assessing disease severity and neurological complications in the acute stage of neuroinfections and can also be useful in evaluating patients with residual symptoms following acute illness.

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: 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.

Background: This study aims to assess the association between lncRNA-NKILA single nucleotide polymorphisms (SNPs) and susceptibility to gastric cancer in the Chinese Han population.

Research design and methods: Four functional SNPs (rs911157, rs16981280, rs2273534, and rs957313) were validated using bioinformatics analysis and genotyped in 490 patients and 490 controls. A case-control study was conducted to analyze the association between NKILA SNPs and gastric cancer risk. qRT-PCR was conducted to detect the NKILA expression in plasma of different rs911157 and rs16981280 genotypes. The effect of rs16981280 C>T mutation on the binding ability of NKILA and miR-6731-5p was verified by dual-luciferase experiment.

Results: In this study, rs911157 CT genotype (OR:1.72, 95%CI:1.20-2.69) was associated with an increased risk of gastric cancer, whereas rs16981280 CG (OR:0.64, 95%CI:0.48-0.85) and GG genotypes (OR:0.56, 95%CI:0.36-0.87) were associated with a reduced risk. The population attributable risk percentage for rs911157 T-carriers was below 10%, while for the rs16981280 CC genotype was approximately 15%. Rs911157 C carried a binding site with miR-6731-5p while T allele might cause the target loss.

Conclusions: In summary, NKILA polymorphism might be related to the susceptibility of gastric cancer. NKILA rs911157 C/T genotype probably affects the function of gastric cancer cells by modulating the interactions with of miR-6731-5p.

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: 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.

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: 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: In the management of breast cancer, the need for assessment of axillary status has been questionable in recent years. However, it is still applicable for making a decision on adjuvant therapy and evaluating the prognosis. Molecular tests have been widely used for intraoperative detection of axillary lymph node metastases and have prevented a second surgery for dissection of the lymph nodes in at least 20% of the cases. Unlike histopathological examination, molecular tests do not need a specialized technologist to provide the results.

Areas covered: We have reviewed recent advancements in the assessment of axillary nodes by molecular studies such as one-step nucleic acid amplification (OSNA) assay and metasin test. Our work concentrated on reported thresholds for the tests, economical aspects, and newly developed devices throughout the current literature.

Expert opinion: Well-designed clinical trials on molecular assays could lead to individualized management of the axillary, while preventing additional surgical operations in a large proportion of women with breast cancer.