Expert Review of Molecular Diagnostics最新文献

Background: The hTERT gene is an essential part of the telomerase enzyme, preserving telomere length and encouraging cellular immortality. The study aimed to investigate whether the TERT gene SNP was associated with an increased risk of lung cancer in the North Indian population.

Research design and methods: 387 lung cancer patients undergoing platinum-based chemotherapy and 384 healthy controls were genotyped for the TERT variant rs2735940 (T>C) using PCR-RFLP. The study aimed to determine the significant association between the TERT genetic variant and lung cancer risk.

Results: Patients carrying homozygous mutant genotype (CC) for rs2735940 showed a significant association (0 R = 2.4, p = 0.03). Furthermore, in dominant model, the combination genotype (TC+CC) showed an increased risk of lung cancer susceptibility with an AOR of 1.67 (p = 0.0016). For TERT rs2735940, individuals with SCLC carrying the mutant genotype (CC) were significantly more likely to develop lung cancer (p = 0.0004). Our results also showed that lung cancer patients carrying the TERT rs2735940 genetic variant who received a combination of docetaxel and cisplatin/carboplatin had better prognosis as compared to alternative chemotherapy regimens.

Conclusion: Our study associates' chemotherapy toxicities in North Indian lung cancer patients and the TERT polymorphism rs2735940, delivering insights for improving biomarker development and individualized 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: 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.

Introduction: Osteoarthritis (OA) involves an inflammatory component, presenting as synovitis and systemic low-grade inflammation. Preliminary evidence suggests that anti-inflammatory treatments may offer symptomatic and structural benefits in OA. More targeted approaches have been proposed and tested, but the means of identifying the clinical and molecular characteristics of patients with an inflammatory subtype remains unclear. Emerging evidence suggests that subsets of OA patients with significant inflammatory features, such as elevated systemic and synovial cytokine levels (e.g. IL-1, TNF-α), imaging confirmed synovitis, or tissue remodeling biomarker signatures may respond more favorably to anti-inflammatory treatments.

Areas covered: We provide a perspective on recent evidence supporting the existence of a clinically actionable inflammatory molecular endotype of OA. We integrate key advances from recent clinical studies, biomarker consortium datasets and imaging models, to outline potential tools for single-patient endotyping, and highlight practical considerations for recognizing an inflammatory endotype in the clinical trial setting.

Expert opinion: Challenges remain in standardizing tools for identifying these patients. Current methodology, including imaging and soluble biomarkers, are not yet been widely adopted in clinical practice. An improved understanding of the inflammatory endotype will be key for improving clinical trial design and identifying patient subpopulations more likely to benefit from targeted treatment.

Introduction: This special report explores the advancements of salivary biomarkers for early detection across various cancer types.

Areas covered: Saliva-based liquid biopsy has emerged as a promising diagnostic tool with a unique capability to capture a wide range of molecular signals that may reflect systemic disease signatures. Novel platforms such as Electric Field-Induced Release and Measurement (EFIRM) and next-generation sequencing (NGS)-based techniques are introduced. This report also addresses the challenges in standardizing saliva collection and biomarkers. Saliva diagnostics hold potential in changing the landscape of cancer detection and disease monitoring. However, barriers in reproducibility, sample variability, and accessibility must be addressed.

Expert opinion: We anticipate that through interdisciplinary collaborations, saliva-based diagnostic tools will be brought to the frontline of clinical practices for routine screening for cancer in the future, opening doors to earlier detection and increased accessibility to precision oncology.

Background: Huntington's disease (HD) is a neurodegenerative condition resulting from CAG trinucleotide expansion in the HTT. 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: 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: 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.