Showing papers in "Expert Review of Molecular Diagnostics in 2018"
TL;DR: There are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome, which could serve as a theranostic tool in facilitating drug development and treatment monitoring.
Abstract: Introduction: Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encourag...
271 citations
TL;DR: This paper will focus on the potential application of ddPCR and optimized NGS to detect ctDNA for detection of cancer recurrence and minimal residual disease as well as early diagnosis of cancer patients.
Abstract: Introduction: Early detection of cancers through the analysis of ctDNA could have a significant impact on morbidity and mortality of cancer patients. However, using ctDNA for early cancer diagnosis...
150 citations
TL;DR: There are considerable barriers to adoption for diagnostic metagenomics, including analytical sensitivity, interpretation, actionability, turnaround time, antimicrobial susceptibility, clinical utility, laboratory workflow, trial comparators, cost, and reimbursement.
Abstract: Introduction: Diagnostic metagenomics and its associated trail of publications are spreading across the world. Multiple clinical labs in the United States, Europe, and Asia have gone to considerabl...
107 citations
TL;DR: The authors discuss the dependency of the breast tumor cells on different components of the microenvironment for their survival, dissemination, dormancy and establishment in secondary sites to form overt metastasis, as well as the potential as a therapeutic target to improve breast cancer outcome.
Abstract: Introduction: Numerous clinical and pre-clinical studies have provided ample evidence supporting that the tumor microenvironment plays a significant role during breast cancer development, progressi...
100 citations
TL;DR: This review will focus on the feasibility of evaluating molecular-based biomarkers in body fluids as markers for diagnosis, prognosis, and surveillance in head and neck squamous cell carcinoma patients.
Abstract: Introduction: Head and neck squamous cell carcinoma (HNSCC) encompasses tumors arising from several locations (oral and nasal cavities, paranasal sinuses, salivary glands, pharynx, and larynx) and currently stands as the sixth most common cancer worldwide. The most important risk factors identified so far are tobacco and alcohol consumption, and, for a subgroup of HNSCCs, infection with high-risk types of human papillomavirus (HPV). Despite several improvements in the treatment of these tumors in the last decades, overall survival rates have only improved marginally, mainly due to the advanced clinical stage at diagnosis and the high rates of treatment failure associated with this late diagnosis.Areas covered: This review will focus on the feasibility of evaluating molecular-based biomarkers (mRNA, microRNA, lncRNA, DNA methylation and protein expression) in body fluids (serum, plasma, and saliva) as markers for diagnosis, prognosis, and surveillance.Expert commentary: The potential use of those m...
97 citations
TL;DR: This review focuses on the different types of circulating RNA biomarkers under investigation, describing the latest advances in their development and application to clinical settings, as well as challenges that researchers face in the process.
Abstract: Introduction: Cancer statistics show that recent improvements in cancer management are only mildly effective in the absence of reliable biomarkers for the detection, diagnosis and monitorin...
78 citations
TL;DR: Novel sensors with new kinds of plasmonic transducers and innovative concepts for the signal development as well as read-out principles were identified and the main trends are expected towards optimal LSPR concepts which represent cost-efficient and robust point-of-care solutions, and the use of multiplexed devices for clinical applications.
Abstract: Introduction: Bioanalytical sensing based on the principle of localized surface plasmon resonance experiences is currently an extremely rapid development. Novel sensors with new kinds of plasmonic ...
67 citations
TL;DR: Metabolomics has been demonstrated as rapidly growing due to the improvements in instrumentation, mainly mass spectrometry, and data mining software and should be validated in different stages, from analytical validation to validation in independent sets of samples, using thousands of samples from different sources.
Abstract: Introduction: Studying changes in the whole set of small molecules, final products of biochemical reactions in living systems or metabolites, is extremely appealing because they represent the best ...
63 citations
TL;DR: The highest frequency of genetic anomalies is observed in severe spermatogenic impairment, which can be treated with in vitro fertilization (IVF), and the diagnosis of known and the discovery of novel genetic factors in idiopathic infertility is of outmost clinical importance.
Abstract: Introduction: Male infertility affects about 7% of the general male population, and it is a multifactorial, polygenic pathological condition. Known genetic factors, accounting for about 20–...
56 citations
TL;DR: The authors found that PMN-MDSC and their function through increased arginase-1 (Arg-1) are associated with MM progression, and are reduced in vivo after lenalidomide but not bortezomib treatment.
Abstract: Objectives: Despite improvement in overall response due to the introduction of the first-in-class proteasome inhibitor bortezomib (btz), multiple myeloma (MM) is still an incurable disease due to t...
54 citations
TL;DR: The authors expect that the incorporation of AR-V7 status and other biomarkers in the sequential assessment of patients with advanced prostate cancer will lead to a more rational use of available and future therapies, with significant improvements in outcomes for patients.
Abstract: Introduction: Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay...
TL;DR: The current status of the molecular diagnostics in the diagnosis of mucormycosis: serologic tests, IHC, PCR, protein-based with MALDI-TOF, metabolomics and metagenomic sequencing are reported.
Abstract: Introduction: Fungal infection burden related to Mucorales has been on the rise with significant associated morbidity and mortality. The major obstacle in the management has been lack of a non-inva...
TL;DR: This review aims to explore the different point-of-care tests currently available to diagnose viral respiratory tract infections, discuss the advantages and limitations of point- of-care testing, and provide insights into the future of point of care tests.
Abstract: Introduction: Successful treatment outcomes for viral respiratory tract infections presenting from primary health care to quaternary hospitals will only be achieved with rapid, sensitive and specif...
TL;DR: This review examines the recent findings, coming from different ‘omic sciences,’ in human blood-based biomarkers associated with antidepressant treatment response with particular attention on genetic/epigenetic and biochemical biomarkers.
Abstract: INTRODUCTION Millions of people worldwide suffer from depression, but despite advances in pharmacological therapies, many patients do not experience symptomatic remission or treatment response, even after treatments with several medications. As such, there is an urgent need to identify biomarkers that can not only predict the treatment response but also allow a rational selection of optimal therapy for each patient. Areas covered: This review examines the recent findings, coming from different 'omic sciences,' in human blood-based biomarkers associated with antidepressant treatment response with particular attention on genetic/epigenetic and biochemical biomarkers. Specific emphasis will be placed on key molecules related to neuroplasticity and inflammation because of their involvement in the pathophysiology of depression and antidepressant response. Expert commentary: Biomarker identification is still an ongoing work. Indeed, to date, no biomarkers have sufficiently proven specificity, sensitivity, and reproducibility to be used in the clinical setting. However, 'omic' approaches hold great promise in identifying multiple features for predicting antidepressant response, making a personalized treatment strategy possible for each patient, and thereby assist with quick and efficacious responsiveness. It is thus necessary that future studies take an integrative approach that includes clinical assessment, environment influences, and molecular and biological biomarkers.
TL;DR: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI and the use of mi RNAs as potential markers of progression of D ILI and specific zonated damage within the liver is discussed.
Abstract: Introduction: Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers.Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI. Furthermore, the use of miRNAs as potential markers of progression of DILI and specific zonated damage within the liver is discussed.Expert commentary: MiRNAs offer more sensitive and specific markers over the current biomarkers for DILI. Combinations of different miRNAs may be able to relay the location of DILI and the progression of...
TL;DR: A review of the literature is presented to update the applicability of cfDNA for diagnosis and monitoring of NSCLC patients and detects somatic alterations in cfDNA, which is already in use in clinical practice and provides valuable information for patient management.
Abstract: Introduction: Collection of tumor samples is not always feasible in non-small cell lung cancer (NSCLC) patients, and circulating free DNA (cfDNA) extracted from blood represents a viable alternative. Different sensitive platforms have been developed for genetic cfDNA testing, some of which are already in clinical use. However, several difficulties remain, particularly the lack of standardization of these methodologies.Areas covered: Here, the authors present a review of the literature to update the applicability of cfDNA for diagnosis and monitoring of NSCLC patients.Expert commentary: Detection of somatic alterations in cfDNA is already in use in clinical practice and provides valuable information for patient management. Monitoring baseline alterations and emergence of resistance mutations is one of the most important clinical applications and can be used to non-invasively track disease evolution. Today, different technologies are available for cfDNA analysis, including whole-genome or exome sequ...
TL;DR: The same liquid biopsy can inform about the status of a tumor and simultaneously evaluate the competency of immune cells to mediate anti-tumor activities and become non-invasive biomarkers of cancer diagnosis, prognosis and response to therapies.
Abstract: Introduction: Liquid biopsy platforms are being actively developed in the biomarker field. Extracellular vesicles (EVs), especially the tumor-derived exosome (TEX) subsets of EVs, represent a platform that allows for molecular and genetic profiling of parent tumor cells. TEX are ubiquitous in body fluids of cancer patients and are promising clinically relevant surrogates of cancer cells. Areas covered: Isolation from body fluids of cancer patients and subsetting of exosomes based on immunoaffinity capture offers a means of evaluating proteins, lipids, nucleic acids and other molecular contents that are a characteristic of TEX and exosomes produced by reprogrammed normal cells. The same liquid biopsy can inform about the status of a tumor and simultaneously evaluate the competency of immune cells to mediate anti-tumor activities. Expert commentary: TEX and reprogrammed non-TEX isolated from plasma of cancer patients have the potential to become non-invasive biomarkers of cancer diagnosis, prognosis and response to therapies.
TL;DR: Digital microfluidics (DMF) technology adds value to the current testing platforms that will benefit apparently healthy newborns with underlying genetic disorders and infants at-risk for conditions that present with symptoms in the newborn period.
Abstract: INTRODUCTION Digital microfluidics (DMF) is an emerging technology with the appropriate metrics for application to newborn and high-risk screening for inherited metabolic disease and other conditions that benefit from early treatment. Areas covered: This review traces the development of electrowetting-based DMF technology toward the fulfillment of its promise to provide an inexpensive platform to conduct enzymatic assays and targeted biomarker assays at the bedside. The high-throughput DMF platform, referred to as SEEKER®, was recently authorized by the United States Food and Drug Administration to screen newborns for four lysosomal storage disorders (LSDs) and is deployed in newborn screening programs in the United States. The development of reagents and methods for LSD screening and results from screening centers are reviewed. Preliminary results from a more compact DMF device, to perform disease-specific test panels from small volumes of blood, are also reviewed. Literature for this review was sourced using principal author and subject searches in PubMed. Expert commentary: Newborn screening is a vital and highly successful public health program. DMF technology adds value to the current testing platforms that will benefit apparently healthy newborns with underlying genetic disorders and infants at-risk for conditions that present with symptoms in the newborn period.
TL;DR: This work provides a framework for selecting biomarkers that are most likely to provide useful information about a patient’s disease state and describes trade-offs between biomarkers’ sensitivity/specificity for a disease-causing agent, the complexity of detection, and how this knowledge can be applied to the development of diagnostic tests.
Abstract: INTRODUCTION Biomarkers are objective indications of a medical state that can be measured accurately and reproducibly. Traditional biomarkers enable diagnosis of disease through detection of disease-specific molecules, disease-mediated molecular changes, or distinct physiological or anatomical signatures. Areas covered: This work provides a framework for selecting biomarkers that are most likely to provide useful information about a patient's disease state. Though the authors emphasize markers related to disease, this work is also applicable to biomarkers for monitoring physiological changes such as ovulation or pregnancy. Additionally, the scope was restricted to biomarkers that are amenable to analytical detection across a range of health care levels, including low resource settings. The authors describe trade-offs between biomarkers' sensitivity/specificity for a disease-causing agent, the complexity of detection, and how this knowledge can be applied to the development of diagnostic tests. This report also details additional assessment criteria for successful tests. Expert commentary: Biomarker selection should primarily be driven by an attempt to answer an explicit clinical question (preferably causative relationship of the biomarker to disease-state), and only then by test development expediency (ease of detection). This framework is useful for stakeholders from test developers to clinicians to identify the trade-offs for diagnostic biomarkers for any use case.
TL;DR: The present manuscript discusses the existing knowledge regarding the involvement of miRNAs and lncRNAs in the molecular background of breast and ovarian malignancies, to highlight their clinical utility in improving disease management.
Abstract: INTRODUCTION The elucidation of tumor molecular hallmarks and the identification of novel molecular markers are of first translational priority in breast and ovarian cancer research, aiming to support personalized disease treatment and monitoring decisions. Recent high-throughput studies have revealed that ~ 80% of the genome is transcribed into RNAs without protein-coding potential, namely non-coding RNAs (ncRNAs), challenging the concept of 'junk DNA'. Undoubtedly, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the best-studied family classes, emerging as the most powerful gene-expression regulators at epigenetic, transcriptional and post-transcriptional levels. Areas covered: Cancer research has highlighted the active implication of ncRNAs, most notably of miRNAs and lncRNAs, in almost every aspect of the cancer cells' biology as well as their deregulated expression in both breast and ovarian tumors. In the present manuscript we discuss the existing knowledge regarding the involvement of miRNAs and lncRNAs in the molecular background of breast and ovarian malignancies, to highlight their clinical utility in improving disease management. Expert commentary: miRNAs and lncRNAs represent central mediators of cancer cells' phenotype, and promising molecular markers and therapeutic targets to support precision medicine in breast and ovarian cancers.
TL;DR: Through the use of machine learning and an unbiased set of features extracted from clinical repositories, researchers will have the potential to further understand complex traits and identify patient subgroups and this knowledge may lead to more preventative and precise clinical care.
Abstract: Introduction: For the past decade, the focus of complex disease research has been the genotype. From technological advancements to the development of analysis methods, great progress has been made....
TL;DR: This review examines what is known about procalcitonin testing in patients with organ dysfunction, including those with end-stage renal disease, congestive heart failure, chronic obstructive pulmonary disease, and cirrhosis, and explores how the assay is now being used in the management of non-infectious diseases.
Abstract: Introduction: Procalcitonin has emerged as a reliable marker of acute bacterial infection in hospitalized patients and the assay has recently been incorporated into several clinical algorithms to r...
TL;DR: Expansion of cell-free fetal DNA analysis to include the transcriptome and the methylome is likely to yield clinical benefits for monitoring other pregnancy-related pathologies such as preeclampsia and intrauterine growth restriction.
Abstract: Introduction: The advent of affordable and rapid next-generation sequencing has been transformative for prenatal diagnosis. Sequencing of cell-free DNA in maternal plasma has enabled the development of not only a highly sensitive screening test for fetal aneuploidies, but now definitive noninvasive prenatal diagnosis for monogenic disorders at an early gestation. Sequencing of fetal exomes offers broad diagnostic capability for pregnancies with unexpected fetal anomalies, improving the yield and accuracy of diagnoses and allowing better counseling for parents. The challenge now is to translate these approaches into mainstream use in the clinic.Areas covered: Here, the authors review the current literature to describe the technologies available and how these have evolved. The opportunities and challenges at hand, including considerations for service delivery, counseling, and development of ethical guidelines, are discussed.Expert commentary: As technology continues to advance, future developments m...
TL;DR: The authors aim to review the importance of rapid and accurate testing for RSV and will describe the available molecular RSV diagnostic assays approved for use at the point-of-care.
Abstract: Introduction: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections. The clinical manifestations of RSV are indistinguishable from other etiologies of acute respirato...
TL;DR: In the present review the authors have discussed a number of novel solutions utilizing a variety of molecular techniques for pathogen detection, identification and antimicrobial susceptibility that have potential to revolutionize diagnosis of BSI.
Abstract: Introduction: The antimicrobial aspect of management of patients with blood stream infections (BSI) and sepsis is time critical. In an era of increasing antimicrobial resistance, rapid detection and identification of bacteria with antimicrobial susceptibility is crucial to direct therapy early in the course of illness. Molecular techniques offer a potential solution to this.Areas covered: In the present review the authors have discussed a number of novel solutions utilizing a variety of molecular techniques for pathogen detection, identification and antimicrobial susceptibility. The review is not designed to be an exhaustive literature review covering all diagnostic solutions ever developed, instead the authors have focused on what they have had experience using, evaluating or currently view as new and exciting with potential to revolutionize BSI diagnosis.The authors searched PubMed (Medline) and Google Scholar with terms: BSI, Bacteraemia, Candidaemia, Diagnostics, AST, Rapid, AMR, Novel and Blo...
TL;DR: In this review, the authors summarize the evolution of array CGH technology from their diagnostic laboratory, highlighting exonic SNP arrays developed in the past decade which detect small intragenic copy number changes as well as large DNA segments for the region of heterozygosity.
Abstract: Introduction: In 2004, the implementation of array comparative genomic hybridization (array comparative genome hybridization [CGH]) into clinical practice marked a new milestone for genetic diagnos...
TL;DR: Certain serum biomarkers, like miR-122, may have clinical utility in early-presenting patients with either intrinsic or idiosyncratic DILI in the future, while others likely will not find use.
Abstract: Introduction: The difficulty of understanding and diagnosing drug-induced liver injury (DILI) has led to proliferation of serum and genetic biomarkers. Many applications of these biomarkers have be...
TL;DR: The role of IDH mutations in clinical practice as a diagnostic, prognostic and predictive biomarker, and as a potential therapeutic target is emphasized and the routine use of noninvasive techniques for detection and monitoring of the IDH status remains challenging.
Abstract: Introduction: Mutations in the genes isocitrate dehydrogenase (IDH) 1 and 2 have been reported in a limited number of tumors. In gliomas, IDH mutations are primarily detected in WHO grade II-III tumors and represent a major biomarker with diagnostic, prognostic, and predictive implications. The recent development of IDH inhibitors and vaccines suggests that the IDH mutation is also an appealing target for therapy. Areas covered: This review focuses on the role of IDH mutations in diffuse gliomas. Besides discussing their role in gliomagenesis, we will emphasize the role of IDH mutations in clinical practice as a diagnostic, prognostic and predictive biomarker, and as a potential therapeutic target. Noninvasive detection of the IDH mutation by means of liquid biopsy and MR spectroscopy will also be discussed. Expert commentary: While IDH mutation is a consolidated diagnostic and prognostic biomarker in clinical practice, its role in oncogenesis is far from being elucidated, and there are several pending issues. The routine use of noninvasive techniques for detection and monitoring of the IDH status remains challenging. Although the IDH mutation is a very early alteration in gliomagenesis, it may then be omitted during tumor progression. This observation has important implications when designing targeted clinical trials.
TL;DR: This review focuses on lessons learned through early attempts of clinically implementingPGx testing; the challenges and opportunities that PGx testing brings to precision medicine in the era of NGS.
Abstract: Introduction: The rapid development and dramatic decrease in cost of sequencing techniques have ushered the implementation of genomic testing in patient care. Next generation DNA sequencing (NGS) t...
TL;DR: Interestingly, mouse models of colorectal cancer injected with bacterial CDDL displayed a reduced response to gemcitabine, but this resistance was neutralized by the antibiotic ciprofloxacin.
Abstract: Introduction: Pancreatic cancer is a complex disease, with an extremely poor response to chemotherapy. Emerging evidence indicates that the tumor microenvironment (TME) might play an important role in mediating chemoresistance. Areas covered: The evaluated study by Geller and collaborators describes several bacterial species within pancreatic tumor tissues and TME and investigated their roles in gemcitabine chemoresistance. Intratumor bacteria express the enzyme cytidine deaminase (CDD), whose long form (CDDL) was shown to metabolize gemcitabine into its inactive metabolite. CDDL is mostly expressed by Gammaproteobacteria and this was among the most common species in pancreatic cancer tissues. Interestingly, mouse models of colorectal cancer injected with bacterial CDDL displayed a reduced response to gemcitabine, but this resistance was neutralized by the antibiotic ciprofloxacin. Expert Commentary: The increased knowledge on the microbiome in pancreatic tissues, as well as its role in chemoresistance, will provide innovative prognostic and therapeutic strategies.