Annals of Laboratory Medicine最新文献

Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease. Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing.

Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N=7), smoldering MM (N=6), and symptomatic MM (N=89).

Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P =0.006), renal insufficiency and NRAS (P =0.012), paramedullary myeloma and TP53 (P =0.02), and extramedullary myeloma and NRAS (P =0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio=7.11, P =0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM.

Conclusions: Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.

Breast cancer is the most common cancer and the second leading cause of cancer death in women worldwide. Novel biomarkers for early diagnosis, treatment, and prognosis in breast cancer are needed and extensively studied. Metabolites, which are small molecules produced during metabolic processes, provide links between genetics, environment, and phenotype, making them useful biomarkers for diagnosis, prognosis, and disease classification. With recent advancements in metabolomics techniques, metabolomics research has expanded, which has led to significant progress in biomarker research. In breast cancer, alterations in metabolic pathways result in distinct metabolomic profiles that can be harnessed for biomarker discovery. Studies using mass spectrometry and nuclear magnetic resonance spectroscopy have helped identify significant changes in metabolites, such as amino acids, lipids, and organic acids, in the tissues, blood, and urine of patients with breast cancer, highlighting their potential as biomarkers. Integrative analysis of these metabolite biomarkers with existing clinical parameters is expected to improve the accuracy of breast cancer diagnosis and to be helpful in predicting prognosis and treatment responses. However, to apply these findings in clinical practice, larger cohorts for validation and standardized analytical methods for QC are necessary. In this review, we provide information on the current state of metabolite biomarker research in breast cancer, highlighting key findings and their clinical implications.

Background: FISH is the standard method for detecting cytogenetic abnormalities (CAs) in patients with multiple myeloma, and pre-enrichment of plasma cells is recommended to increase detection rates. However, optimal strategies to ensure sufficient plasma cell retrieval when standard enrichment techniques fail remain underexplored. We investigated factors influencing the success of fluorescence-activated cell sorting (FACS) and assessed the use of direct FISH in cases in which FACS failed.

Methods: A retrospective analysis was conducted on 457 bone marrow samples submitted for FISH between November 2016 and May 2022. FACS was considered successful when plasma cells (CD38+ and CD138+ cells) constituted >1% of the total number of cells. Direct FISH was performed for samples with FACS failure.

Results: FACS was successful in 70.9% of cases and had a high positivity rate (94.8%). Shorter sample transfer times significantly improved FACS success, with a 77.1% success rate for transfer times <2 hrs, compared with 67.8% for longer times (P =0.0388). Plasma cell percentage was a strong determinant of FACS success, with a median of 31.2% in successful cases versus 8.5% in failures (P <0.0001). Even when FACS failed, direct FISH detected CAs in 43.6% of cases.

Conclusions: Plasma cell percentage and sample transfer time are critical factors influencing FACS success. While FACS-FISH demonstrates superior sensitivity in detecting CAs, direct FISH serves as a valuable alternative when FACS fails. These findings highlight the importance of optimizing sample handling and FISH protocols for accurate cytogenetic analysis of multiple myeloma.

Despite primary glomerulonephritis (PGN) being a leading cause of chronic kidney disease and end-stage renal disease, specific and sensitive biomarkers for the early detection and monitoring of this condition are lacking. We evaluated the value of the combined detection of serum cystatin C (CYSC), β2-microglobulin (β2-MG), and urine transferrin (TRF) for diagnosing early-stage PGN. From May 2021 to May 2023, we enrolled 105 patients in our hospital as the observation group and 50 healthy volunteers as the control group. Their serum expression levels of CYSC, β2-MG, and TRF were evaluated. We plotted separate ROC curves and calculated the area under the curve (AUC) values of CYSC, β2-MG, and TRF to assess their diagnostic performance in PGN. The levels of CYSC, β2-MG, and TRF were significantly higher (P <0.05) in the observation group than in the healthy control group. CYSC, β2-MG, and TRF were expressed at significantly higher levels in G2, G3a, and G3b of PGN than in G1. The combined use of CYSC, β2-MG, and TRF as biomarkers could significantly improve the early diagnosis and monitoring of PGN and may lead to better patient outcomes by facilitating earlier intervention and treatment strategies.

Background: Understanding the virulence and pathogenicity of invasive nontyphoidal Salmonella (iNTS) in children may support timely treatment and enable closer monitoring of chronic infections. iNTS epidemiology in Asia remains inadequately described. We analyzed the genetic diversity and virulence genes associated with extra-intestinal invasion in Korean children.

Methods: Salmonella isolates from children <18 yrs of age diagnosed with moderate-to-severe salmonellosis between January 2019 and December 2021 were subjected to antibiotic susceptibility testing and whole-genome sequencing.

Results: In total, 58 cases were included. We identified 20 serotypes, the most prevalent being Salmonella Enteritidis (N=21), followed by Infantis (N=6), I 4,[5],12:i:- (N=5), and Bareilly (N=5). Extra-intestinal invasion occurred in 12 (20.7%) cases involving Salmonella Oranienburg (2/2), Give (1/1), Javiana (1/1), Paratyphi B var. L(+) tartrate+ (1/1), Schwarzengrund (1/1), Singapore (1/1), Montevideo (1/2), Saintpaul (1/2), I 4:b:- (1/2), Infantis (1/6), and Enteritidis (1/21). While the numbers of total virulence genes and genes belonging to major virulence categories did not significantly differ between iNTS and non-iNTS, several genetic factors, including Salmonella pathogenicity island (SPI)-1 (P =0.039), SPI-2 (P =0.020), SPI-5 (P =0.014), SPI-13 (P =0.010), cytolethal distending toxin-related genes (P =1.4×10^-4), fepC (P =0.021), and tcpC (P =0.040) were more frequent in invasive isolates.

Conclusions: Salmonella Enteritidis-ST11 predominated in infections among Korean children, but invasive isolates were rare. Early detection of genetic factors associated with extra-intestinal invasion will be helpful for prompt and appropriate treatment.