Expert Review of Molecular Diagnostics最新文献

Introduction: Faster turnaround times can lead to rapid patient treatment. Implementing a point-of-care (POC) molecular COVID-19 test requires careful planning. In the POC setting, there are numerous operators and regular monitoring of their activities is key to the successful implementation of a POC molecular test. Test errors can arise from samples, operators, reagents, the testing system, and even from the environment. These sources of error should be considered when implementing a new test.

Areas covered: We outline the importance of establishing well-defined policies for staff to follow at the preanalytic, analytic and postanalytic phases of SARS-CoV-2 testing. As these factors are crucial for the accuracy and reliability of the test results. The key discussion points are from the CLSI EP23-Ed2 document on developing individualized quality control plans and medical literature search engines such as EMBASE, MEDLINE and MedlinePlus.

Expert opinion: The risk management principles applied when implementing nucleic acid POC tests can identify specific control processes to help mitigate common sources of error when conducting molecular testing at the POC.

Background: Gastric cancer (GC) is one of the most common types of cancer worldwide. Recent studies have shown that tsRNAs play important roles in GC and that changes in the expression levels of tsRNAs can be used for GC diagnosis and treatment response prediction.

Research design and methods: Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the correlation between tsRNA expression and prognosis and other clinicopathologic features of GC patients. The sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were analyzed to evaluate the diagnostic value of tsRNAs.

Results: The results showed that patients with tsRNA upregulation had a poor prognosis (HR = 2.48, 95% CI: 1.85-3.34), while patients with tsRNA downregulation had a favorable prognosis (HR = 0.55, 95% CI: 0.31-0.98). In addition, tsRNA expression was significantly correlated with various clinicopathological features in patients with GC. Finally, in diagnostic studies, GC-related tsRNAs could differentiate healthy controls (AUC = 0.81, DOR = 7.74) from patients with inflammation (AUC = 0.74, DOR = 4.44).

Conclusions: tsRNAs have potential clinical application in GC diagnosis and prognosis evaluation. It is necessary to further assess and verify the practicability and feasibility of additional specific tsRNAs as GC markers in the future.

Background: To observe the level of serum Sema7A in acute aortic dissection (AAD) and its diagnostic value for AAD.

Research design and methods: Patients with sudden chest pain including AAD, acute myocardial infarction (AMI) or pulmonary embolism (PE) were enrolled. Patients without chest pain or cardiovascular diseases were included as the controls. Serum Sema7A and plasma D-dimer were detected and compared in each group.

Results: 85 AAD patients, 55 AMI patients, 15 PE patients, and 30 controls were enrolled. The concentration of Serum Sema7A in the AAD group was significantly higher than that in the control, AMI and PE group. Serum Sema7A was positively correlated with D-dimer. In AAD patients who underwent invasive intervention therapy, serum Sema7A levels were significantly decreased after the intervention. Serum Sema7A was an independent risk factor for the presence of AAD. The areas under the ROC curve of Sema7A and D-dimer for differential diagnosis of AAD from other chest pain disorders were 0.842 (0.776, 0.909) and 0.788 (0.714, 0.862), respectively.

Conclusions: Sema7A is highly expressed in patients with AAD. Sema7A might be a valuable biomarker for the early diagnosis of AAD and has the potential to differentiate AAD from AMI and PE.

Introduction: The advance of diagnostics and treatments has greatly improved the prognosis of non-small cell lung cancer (NSCLC) patients. However, relapse and metastasis are still common problems encountered by NSCLC patients who have achieved complete remission. Therefore, overcoming the challenge of relapse and metastasis is particularly important for improving the prognosis of NSCLC patients. Research has shown that minimal residual disease (MRD) was a potential source of tumor relapse and metastasis, and circulating tumor DNA (ctDNA) MRD has obvious advantages in predicting the relapse and metastasis of NSCLC and evaluating treatment effectiveness. Therefore, dynamic monitoring of MRD is of great significance for NSCLC patient management strategies.

Areas covered: We have reviewed articles related to NSCLC MRD included in PubMed and describes the biological significance and historical context of MRD research, reasons for using ctDNA to evaluate MRD, and potential value and challenges of ctDNA MRD in assessing relapse and metastasis of NSCLC, ultimately guiding clinical therapeutic strategies and management.

Expert opinion: The standardized scope of ctDNA MRD detection for NSCLC requires more clinical research evidence to minimize study differences, making it possible to include in the clinical staging as a reliable indicator.

Introduction: Bladder cancer (BCa) is the most frequent cancer of the urinary tract, with more than 500,000 reported cases and nearly 200,000 related deaths yearly. Cystoscopy is the standard examination used for the initial diagnosis and follow-up of BCa in the noninvasive stage. However, the American Cancer Society does not include BCa screening in its list of recommended cancer screenings.

Areas covered: Recently, several urine-based bladder tumor markers (UBBTMs) that identify genomic, transcriptomic, epigenetic, or protein alterations have been introduced, some of which have been approved by the Food and Drug Administration (FDA) to improve its diagnosis and surveillance. Several biomarkers have been found in the tissues and blood of individuals with BCa or predisposed to develop the disease, further enriching our information.

Expert opinion: From a prevention perspective, alkaline Comet-FISH could be a valuable tool with broad potential for clinical application. Furthermore, a comet assay could be more beneficial for diagnosing and monitoring bladder cancer and determining individual susceptibility. Thus, we recommend further studies to understand the potential of this combined assay in the general population as a potential screening test and in patients initiated into the diagnostic process.

Objective: To assess the diagnostic accuracy of noninvasive prenatal screening (NIPS) in screening for copy number variations (CNVs).

Methods: We conducted a systematic review and meta-analysis by combining our study results with those reported in other articles. We retrospectively collected the data of pregnant women with NIPS testing in the Hangzhou Women's Hospital from December 2019 to February 2022. Simultaneously, a systematic search of PubMed, EMBASE, and Web of Science was carried out to identify all relevant peer-reviewed publications. Statistical analysis was performed based on the random-effects model to determine a pooled estimate of the positive predictive value (PPV).

Results: A total of 29 studies involving 2,667 women were included for analysis. The pooled PPV of NIPS in the detection of CNVs was 32.86% (95% confidence interval [24.61-41.64]). Statistical heterogeneity was high, while no significant publication bias was found in this meta-analysis. There were insufficient data to accurately determine sensitivity and specificity, as most studies only performed confirmatory tests on high-risk women.

Conclusions: The PPV of NIPS in screening for CNVs was approximately 33%. Cautions should be kept in mind for the pretest guidance and subsequent after-test counseling when offering such genome-wide NIPS tests.

Introduction: Exportin 1 (XPO1) is overexpressed in several solid tumors, and is associated with poor prognosis. Here, we aimed to evaluate the implication of XPO1 expression in solid tumors through a meta-analysis.

Methods: PubMed, Web of Science, and Embase databases were searched for articles published until February 2023. Statistical data of the patients, odds ratios and hazard ratios (HRs), together with their corresponding 95% confidence intervals (CIs) were pooled to assess clinicopathological features and survival outcomes. Besides, the Cancer Genome Atlas (TCGA) was used to explore the prognostic significance of XPO1 in solid tumors.

Results: A total of 22 works, comprising 2595 patients were included in this study. The results suggested that increased XPO1 expression was associated with a higher tumor grade, more lymph node metastasis, advanced tumor stage, and progressively worse total clinical stage. Additionally, high XPO1 expression was associated with worse overall survival (OS) (HR = 1.43, 95% CI = 1.12-1.81, P = 0.004) and shorter progression-free survival (HR = 1.40, 95% CI = 1.07-1.84, P = 0.01). An analysis using the TCGA dataset showed that high XPO1 expression was associated with poor OS and disease-free survival.

Conclusions: XPO1 is a promising prognostic biomarker and may constitute a therapeutic target for solid tumors.PROSPERO registration number: CRD42023399159.

Introduction: Breast cancer (BC) is a major public health concern, and identifying new biomarkers and therapeutic targets is critical to improving patient outcomes. MALAT1, a long noncoding RNA, has emerged as a promising candidate due to its overexpression in BC and the associated poor prognosis. Understanding the role of MALAT1 in BC progression is paramount for the development of effective therapeutic strategies.

Covered area: This review delves into the structure and function of MALAT1, and examines its expression pattern in breast cancer (BC) and its association with different BC subtypes. This review focuses on the interactions between MALAT1 and microRNAs (miRNAs) and the various signaling pathways involved in BC. Furthermore, this study investigates the influence of MALAT1 on the BC tumor microenvironment and the possible influence of MALAT1 on immune checkpoint regulation. This study also sheds light the role of MALAT1 in breast cancer resistance.

Expert opinion: MALAT1 has been shown to play a key role in the progression of BC, highlighting its importance as a potential therapeutic target. Further studies are needed to elucidate the underlying molecular mechanisms by which MALAT1 contributes to the development of BC. In combination with standard therapy, there is a need to evaluates the potential of treatments targeting MALAT1, which may lead to improved treatment outcomes. Moreover, study of MALAT1 as a diagnostic and prognostic marker promises improved BC management. Continued efforts to decipher the functional role of MALAT1 and explore its clinical utility are critical to advancing the BC research field.

Background: Microsatellite instability (MSI) analysis of tumors informs Lynch syndrome testing, therapeutic choice, and prognosis. The status of MSI is mainly detected by polymerase chain reaction coupled with capillary electrophoresis. However, there are various assays with different detection loci and the obtained results may vary. The objective of this study was to evaluate the concordance among different assays and the performance among different laboratories.

Methods: External quality assessment (EQA) for the detection of MSI was performed in 2021 and 2022. Each sample panel consisted of five samples, including microsatellite-stable and MSI tumor tissues. The sample panels were coded at random, and the returned results were compared and scored.

Results: The fully validated sample panels showed appropriate applicability with commercially available assays. There were eight false-negative results in 2021 and five false results (two false-positives and three false-negatives) in 2022. Among the participating laboratories, in 2021, 20 (74.07%) provided completely correct results; in 2022, 38 (92.68%) obtained an optimal score.

Conclusion: The molecular detection of MSI in China exhibited an improvement in a 2-year EQA study. Participation in EQA program is an efficient way of assessing the performance of laboratories and improving their ability.

Introduction: Lung cancer is a leading cause of death in patients with cancer. Early diagnosis is crucial to improve the prognosis of patients with lung cancer. Plasma circulating cell-free DNA (cfDNA) contains comprehensive genetic and epigenetic information from tissues throughout the body, suggesting that early detection of lung cancer can be done non-invasively, conveniently, and cost-effectively using high-sensitivity techniques such as sequencing.

Areas covered: In this review, we summarize the latest technological innovations, coupled with next-generation sequencing (NGS), regarding genomic alterations, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer, as well as their clinical advances. Additionally, we discuss the suitability of study designs for diagnostic accuracy evaluation for different target populations and clinical questions.

Expert opinion: Currently, cfDNA-based early screening and diagnosis of lung cancer faces many challenges, such as unsatisfactory performance, lack of quality control standards, and poor repeatability. However, the progress of several large prospective studies employing epigenetic features has shown promising predictive performance, which has inspired cfDNA sequencing for future clinical applications. Furthermore, the development of multi-omics markers for lung cancer, including genome-wide methylation and fragmentomics, is expected to play an increasingly important role in the future.