Expert Review of Molecular Diagnostics最新文献

Background: The pathogenesis of lipodystrophy in people living with HIV (PLWHIV) receiving antiretrovirals appears to be multifactorial and may involve genetic factors; however, it is not yet fully understood. We verified the association between single nucleotide polymorphisms in the APOC3-rs2854116, ESR2-rs3020450, HFE-rs1799945 and MMP1-rs1799750 genes and lipodystrophy and its subtypes in PLWHIV receiving antiretroviral.

Methods: Design: cross-sectional study. Lipodystrophy definition was based on self-report. Genotyping of the polymorphisms was performed using real-time polymerase chain reaction.

Results: Lipodystrophy was reported in 204/404 participants (51%), being 89/204 with mixed lipodystrophy, 72/204 with lipohypertrophy, and 43/204 with lipoatrophy. There was no association between APOC3, HFE, and MMP1 polymorphisms and lipodystrophy. The frequency of AA genotype (p=0.004/OR=3.33/CI=1.52-7.29) and of A allele (p=0.031/OR=1.72/CI=1.08-2.75) of the ESR2 polymorphism was higher in individuals with lipoatrophy compared to those without lipodystrophy. In the multivariate analysis, viral load >40copies/mL (p=0.037/OR=2.52/CI=1.03-6.91) and current use of zidovudine (p=0.007/OR=2.97/CI=1.32-6.54) were associated with lipoatrophy.

Conclusion: Participants with lipoatrophy had higher frequency of the AA genotype and the A allele of the ESR2-rs3020450 polymorphism. In addition, viral load >40 copies/mL and current use of zidovudine were associated with lipoatrophy, suggesting a potential involvement of this genetic variant in the pathogenesis of lipoatrophy in PLWHIV receiving antiretroviral.

Introduction: Calcifying carotid artery atheromas (CCAAs) identified on standard dental panoramic radiographs (DPRs) have been presented as potential disease markers for cardiovascular disease (CVD). CCAAs are further linked to several systemic disease processes (i.e. diabetes) that are also associated with periodontitis. The active matrix metalloproteinase-8 (aMMP-8) mouthrinse point-of-care-test has been extensively validated for periodontitis disease diagnostics. Calprotectin can inhibit matrix metalloproteinases and also exert significant anti-microbial activities. Recently, calprotectin has been suggested as a potential biomarker of endovascular inflammation.

Areas covered: This special report considers a combination of mouthrinse aMMP-8 and calprotectin in periodontitis disease diagnostics at the dentist's office for simultaneously identifying patients at risk of diabetes and CVD reviewing recent PubMed indexed findings comparing disease diagnostics by aMMP-8 and calprotectin individually and combined.

Expert opinion: Combining CCAA-DPRs analysis with oral fluid mouthrinse aMMP-8 and calprotectin lateral-flow immunoassays as point-of-care or chair-side tests, especially by polynomial algorithm-based machine learning technologies (including computer vision), can provide a modern, noninvasive, safe, and economical AI-based diagnostic tool. This tool can be utilized for online real-time screening of interlinked processes involving stroke, CVD, diabetes, and periodontal disease cascades. Accordingly, identified at-risk patients are then referred for necessary medical and dental interventions.

Introduction: The urothelium of the upper tract (renal pelvis and ureter) has morphological and functional similarities to the bladder. There are also morphological similarities between the urothelial carcinoma of the upper tract (UTUC) and the bladder (UCB). However, there are differences in the embryological origin, phenotype, disease course, and response to treatment between the upper tract and bladder urothelium and their corresponding malignancies. Comprehensive genomic studies can provide valuable information about the differences between UTUC and UCB, which have diagnostic and therapeutic implications.

Areas covered: In this study, we have collected and compared the available literature on the next-generation sequencing (NGS) of the UTUC and compared it to UCB with a focus on the effect of genomic changes on the disease course and management. The review revealed the value of NGS in providing important information for diagnosis and management, which can result in more successful precision medicine.

Expert opinion: Although there are shared gene alterations between UTUC and UCB, the presence of minor genomic variations between the two site differences in the genomic alterations can explain differences in disease course. An upfront knowledge of the molecular alterations in UTUC can provide valuable information for patient care.

Introduction: Cancer is a significant health problem worldwide, emphasizing the need for new diagnostic techniques. Among various molecular techniques, loop-mediated isothermal amplification (LAMP) has gained growing interest due to its rapidity, sensitivity, and cost-effectiveness.

Areas covered: This review discusses the use of LAMP to target genes as a biomarker for cancer detection. We performed an extensive literature search to identify relevant oncology studies on LAMP. We highlighted its working principles, advantages over conventional diagnostic methods, and potential limitations in clinical settings.

Expert opinion: LAMP has been reported to be an effective molecular diagnostic technique with tremendous improvements in speed, sensitivity, and affordability. Its potential as a diagnostic tool for cancer detection can provide a viable alternative to conventional diagnostic methods, particularly in low-resource environments. However, challenges such as primer design complexity, possibility of false-positive signals, and standardization issues present hindrances to clinical application. Further research and development are required for further refinement and integration into routine diagnostics. Furthermore, integrating LAMP with other molecular technologies and new platforms may render it increasingly useful in the clinical setting. Continuing research in this field is important for establishing the overall efficacy of LAMP in oncology.

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.