Expert Review of Molecular Diagnostics最新文献

Background: The expression of CYP19A1 has implications for the prognosis of female bladder cancer. However, this study aimed to explore the association between single nucleotide polymorphisms (SNPs) in CYP19A1 and bladder cancer risk, as no prior research has addressed this association.

Research design and methods: We selected and genotyped five CYP19A1 SNPs (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) in 217 patients and 550 controls using the Agena MassARRAY system. Logistic regression analysis was employed to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Bioinformatics predicted SNP functions and CYP19A1 involving pathways.

Results: Our study revealed a significant association between bladder cancer risk and four SNPs (rs4646 (AC vs. CC: OR = 1.71, FDR-p = 0.005), rs6493487 (G vs. A: OR = 0.68, FDR-p = 0.011), rs1062033 (G vs. C: OR = 0.36, FDR-p < 0.001), and rs17601876 (GA vs. GG: OR = 1.66, FDR-p = 0.008)) in CYP19A1. The three SNPs (rs4646, rs1062033, and rs17601876) were significantly correlated with CYP19A1 expression levels in normal whole blood (p < 0.05). Moreover, CYP19A1 was found to primarily participate in the steroid hormone biosynthesis and metabolic pathways.

Conclusions: Consequently, CYP19A1 gene polymorphisms may play a crucial role in the genetic susceptibility to bladder cancer.

Introduction: Colon cancer, ranked as the fourth leading global cause of cancer death, exhibits a complex progression marked by genetic variations. Over the past decade, the utilization of diverse CRISPR systems has propelled accelerated research into colorectal cancer (CRC) treatment.

Areas covered: CRISPR/Cas9, a key player in this research, identifies new oncogenes, tumor suppressor genes (TSGs), and drug-resistance genes. Additionally, it facilitates the construction of experimental models, conducts genome-wide library screening, and develops new therapeutic targets, especially for targeted knockout in vivo or molecular targeted drug delivery, contributing to personalized treatments and significantly enhancing the care of colon cancer patients. In this review, we provide insights into the mechanism of the CRISPR/Cas9 system, offering a comprehensive exploration of its applications in CRC, spanning screening, modeling, gene functions, diagnosis, and gene therapy. While acknowledging its transformative potential, the article  highlights the challenges and limitations of CRISPR systems.

Expert opinion: The application of CRISPR/Cas9 in CRC research provides a promising avenue for personalized treatments. Its potential for identifying key genes and enabling experimental models and genome-wide screening enhances patient care. This review underscores the significance of CRISPR-Cas9 gene editing technology across basic research, diagnosis, and the treatment landscape of colon cancer.

Introduction: Community-acquired pneumonia (CAP) is an infectious disease associated with high mortality worldwide. Although Streptococcus pneumoniae remains the most frequent pathogen in CAP, data from recent studies using molecular tests have shown that respiratory viruses play a key role in adults with pneumonia. The impact of difficult-to-treat pathogens on the outcomes of pneumonia is also important even though they represent only a small proportion of overall cases. Despite improvements in the microbiological diagnosis of CAP in recent decades, the identification of the causative pathogen is often delayed because of difficulties in obtaining good-quality sputum samples, issues in transporting samples, and slow laboratory processes. Therefore, the initial treatment of CAP is usually empirical. Point-of-care testing (POCT) was introduced to avoid treatment delays and reduce reliance on empirical antibiotics.

Areas covered: This review summarizes the main scientific evidence on the role of POCT in the diagnosis and management of patients with CAP. The authors searched for articles on POCT in pneumonia on PubMed from inception to 20 January 2024. The references in the identified articles were also searched.

Expert opinion: POCT involves rapid diagnostic assays that can be performed at the bedside especially in cases of severe CAP and immunocompromised patients. These tests can produce results that could help guide initial therapy and management.

Introduction: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition.

Areas covered: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD.

Expert opinion: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.

Introduction: Carbapenem-resistant Enterobacterales (CRE) causing severe infections in humans have represented an important challenge for clinicians worldwide during the past two decades.

Areas covered: Novel β-lactams and β-lactam/β-lactamase inhibitor combinations have led to a shift in the first-line approach to the treatment of severe CRE infections from polymyxin-based regimens to treatment with less toxic agents. This new scenario offers the opportunity to apply rapid molecular diagnostic tests for CRE infection to identify different types of carbapenemases. Herein, the authors provide an overview of this subject and follow it with their expert perspectives.

Expert opinion: When considering studies actually measuring the clinical impact of rapid molecular tests in real-life scenarios, high certainty evidence from randomized controlled trials is still limited and not focused on CRE infections. Nonetheless, it is indisputable that rapid molecular tests have been shown to impact early therapeutic choices (in terms of both escalation and de-escalation) when used in real-life settings, thus issues in the clinical interpretation of their results are already relevant. Overall, increased expertise is required for the appropriate interpretation of rapid molecular tests for personalized antibiotic selection by understanding their strengths and limitations.

Introduction: Theranostics targeting prostate-specific membrane antigen (PSMA) represent a new targeted approach for prostate cancer care that combines diagnostic and therapeutic radiopharmaceuticals to diagnose and treat the disease. Positron emission tomography (PET) is the imaging method of choice and several diagnostic radiopharmaceuticals for quantifying PSMA have received FDA approval and are in clinical use. [⁶⁸Ga]Ga-PSMA-11 is one such imaging agent and the focus of this article. One beta-emitting radioligand therapy ([¹⁷⁷Lu]Lu-PSMA-617) has also received FDA approval for prostate cancer treatment, and several other alpha- and beta-emitting radioligand therapies are in clinical trials.

Areas covered: Theranostics targeting PSMA in men with prostate cancer are discussed with a focus on use of [⁶⁸Ga]Ga-PSMA-11 for imaging PSMA-positive lesions in men with prostate cancer. The review covers [⁶⁸Ga]Ga-PSMA-11 manufacture, current regulatory status, comparison of [⁶⁸Ga]Ga-PSMA-11 to other imaging techniques, clinical updates, and emerging applications of artificial intelligence for [⁶⁸Ga]Ga-PSMA-11 PET.

Expert opinion: [⁶⁸Ga]Ga-PSMA-11 is used in conjunction with a PET/CT scan to image PSMA positive lesions in men with prostate cancer. It is manufactured by chelating precursor with⁶⁸Ga, either from a generator or cyclotron, and has regulatory approval around the world. It is widely used clinically in conjunction with radioligand therapies like [¹⁷⁷Lu]Lu-PSMA-617.

Introduction: In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways.

Areas covered: This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types.

Expert opinion: Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored.

Introduction: Defining the chromosomal and molecular changes associated with myeloid neoplasms (MNs) optimizes clinical care through improved diagnosis, prognosis, treatment planning, and patient monitoring. This review will concisely describe the techniques used to profile MNs clinically today, with descriptions of challenges and emerging approaches that may soon become standard-of-care.

Areas covered: In this review, the authors discuss molecular assessment of MNs using non-sequencing techniques, including conventional cytogenetic analysis, fluorescence in situ hybridization, chromosomal genomic microarray testing; as well as DNA- or RNA-based next-generation sequencing (NGS) assays; and sequential monitoring via digital PCR or measurable residual disease assays. The authors explain why distinguishing somatic from germline alleles is critical for optimal management. Finally, they introduce emerging technologies, such as long-read, whole exome/genome, and single-cell sequencing, which are reserved for research purposes currently but will become clinical tests soon.

Expert opinion: The authors describe challenges to the adoption of comprehensive genomic tests for those in resource-constrained environments and for inclusion into clinical trials. In the future, all aspects of patient care will likely be influenced by the adaptation of artificial intelligence and mathematical modeling, fueled by rapid advances in telecommunications.

Introduction: Despite recent advances in diagnostic technologies and new drugs becoming available, tuberculosis (TB) remains a major global health burden. If detected early, screened for drug resistance, and fully treated, TB could be easily controlled.

Areas covered: Here the authors discuss M. tuberculosis culture methods which are considered the definitive confirmation of M. tuberculosis infection, and limited advances made to build on these core elements of TB laboratory diagnosis. Literature searches showed that molecular techniques provide enhanced speed of turnaround, sensitivity, and richness of data. Sequencing of the whole genome, is becoming well established for identification and inference of drug resistance. PubMed® literature searches were conducted (November 2022-March 2024).

Expert opinion: This section highlights future advances in diagnosis and infection control. Prevention of prolonged hospital admissions and rapid TAT are of the most benefit to the overall patient experience. Host transcriptional blood markers have been used in treatment monitoring studies and, with appropriate evaluation, could be rolled out in a diagnostic setting. Additionally, the MBLA is being incorporated into latest clinical trial designs. Whole genome sequencing has enhanced epidemiological evidence. Artificial intelligence, along with machine learning, have the ability to revolutionize TB diagnosis and susceptibility testing within the next decade.