Molecular Diagnosis & Therapy最新文献

{"title":"Developing a DNA Methylation Signature to Differentiate High-Grade Serous Ovarian Carcinomas from Benign Ovarian Tumors.","authors":"Douglas V N P Oliveira, Edyta Biskup, Colm J O'Rourke, Julie L Hentze, Jesper B Andersen, Claus Høgdall, Estrid V Høgdall","doi":"10.1007/s40291-024-00740-y","DOIUrl":"10.1007/s40291-024-00740-y","url":null,"abstract":"<p><strong>Introduction: </strong>Epithelial ovarian cancer (EOC) represents a significant health challenge, with high-grade serous ovarian cancer (HGSOC) being the most common subtype. Early detection is hindered by nonspecific symptoms, leading to late-stage diagnoses and poor survival rates. Biomarkers are crucial for early diagnosis and personalized treatment OBJECTIVE: Our goal was to develop a robust statistical procedure to identify a set of differentially methylated probes (DMPs) that would allow differentiation between HGSOC and benign ovarian tumors.</p><p><strong>Methodology: </strong>Using the Infinium EPIC Methylation array, we analyzed the methylation profiles of 48 ovarian samples diagnosed with HGSOC, borderline ovarian tumors, or benign ovarian disease. Through a multi-step statistical procedure combining univariate and multivariate logistic regression models, we aimed to identify CpG sites of interest.</p><p><strong>Results and conclusions: </strong>We discovered 21 DMPs and developed a predictive model validated in two independent cohorts. Our model, using a distance-to-centroid approach, accurately distinguished between benign and malignant disease. This model can potentially be used in other types of sample material. Moreover, the strategy of the model development and validation can also be used in other disease contexts for diagnostic purposes.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"821-834"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.","authors":"Pasqualina Colella","doi":"10.1007/s40291-024-00733-x","DOIUrl":"10.1007/s40291-024-00733-x","url":null,"abstract":"<p><p>Pompe disease is a neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), hydrolyzing glycogen to glucose. Pathological glycogen storage, the hallmark of the disease, disrupts the metabolism and function of various cell types, especially muscle cells, leading to cardiac, motor, and respiratory dysfunctions. The spectrum of Pompe disease manifestations spans two main forms: classical infantile-onset (IOPD) and late-onset (LOPD). IOPD, caused by almost complete GAA deficiency, presents at birth and leads to premature death by the age of 2 years without treatment. LOPD, less severe due to partial GAA activity, appears in childhood, adolescence, or adulthood with muscle weakness and respiratory problems. Since 2006, enzyme replacement therapy (ERT) has been approved for Pompe disease, offering clinical benefits but not a cure. However, advances in early diagnosis through newborn screening, recognizing disease manifestations, and developing improved treatments are set to enhance Pompe disease care. This article reviews recent progress in ERT and ongoing translational research, including the approval of second-generation ERTs, a clinical trial of in utero ERT, and preclinical development of gene and substrate reduction therapies. Notably, gene therapy using intravenous delivery of adeno-associated virus (AAV) vectors is in phase I/II clinical trials for both LOPD and IOPD. Promising data from LOPD trials indicate that most participants met the criteria to discontinue ERT several months after gene therapy. The advantages and challenges of this approach are discussed. Overall, significant progress is being made towards curative therapies for Pompe disease. While several challenges remain, emerging data are promising and suggest the potential for a once-in-a-lifetime treatment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"703-719"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.","authors":"Najah Elmounedi, Walid Bahloul, Hassib Keskes","doi":"10.1007/s40291-024-00729-7","DOIUrl":"10.1007/s40291-024-00729-7","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IDD) is one of the most frequent causes of low back pain. No treatment is currently available to delay the progression of IDD. Conservative treatment or surgical interventions is only used to target the symptoms of IDD rather than treat the underlying cause. Currently, numerous potential therapeutic strategies are available, including molecular therapy, gene therapy, and cell therapy. However, the hostile environment of degenerated discs is a major problem that has hindered the clinical applicability of such approaches. In this regard, the design of drugs using alternative delivery systems (macro-, micro-, and nano-sized particles) may resolve this problem. These can protect and deliver biomolecules along with helping to improve the therapeutic effect of drugs via concentrating, protecting, and prolonging their presence in the degenerated disc. This review summarizes the research progress of diagnosis and the current options for treating IDD.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"745-775"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is There a Role for FAPI PET in Urological Cancers?","authors":"Naima Ortolan, Luca Urso, Ilaria Zamberlan, Luca Filippi, Nicolò Maria Buffi, Corrado Cittanti, Licia Uccelli, Mirco Bartolomei, Laura Evangelista","doi":"10.1007/s40291-024-00735-9","DOIUrl":"10.1007/s40291-024-00735-9","url":null,"abstract":"<p><p>This work aims to investigate the utility of positron emission tomography/computed tomography (PET/CT) with fibroblast activation protein inhibitors (FAPI) in urological neoplasms, including prostate cancer, urothelial carcinoma, and renal cell carcinoma. Although the available data are very preliminary, FAPI PET showed potential for detecting primary prostate cancer with low prostate-specific membrane antigen expression, while prostate-specific membrane antigen PET/CT outperformed FAPI PET/CT in detecting biochemical recurrence. In urothelial carcinoma, FAPI PET/CT demonstrated increased detection rates compared with deoxy-2-[18F]fluoro-D-glucose PET/CT, in particular in small lymph node metastases, whose identification is still an unmet clinical need. Limited data are available for renal cell carcinoma. In conclusion, FAPI PET emerges as a promising imaging modality for urological neoplasms, in particular bladder cancer. Further research is warranted to establish its role in guiding therapeutic decisions and as a potential novel theranostic agent.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"721-725"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Complexity: Exploration of Acute Lymphoblastic Leukemia at the Single Cell Level.","authors":"Margo Aertgeerts, Sarah Meyers, Sofie Demeyer, Heidi Segers, Jan Cools","doi":"10.1007/s40291-024-00739-5","DOIUrl":"10.1007/s40291-024-00739-5","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL originates from precursor lymphocytes that acquire multiple genomic changes over time, including chromosomal rearrangements and point mutations. While a large variety of genomic defects was identified and characterized in ALL over the past 30 years, it was only in recent years that the clonal heterogeneity was recognized. Thanks to the latest advancements in single-cell sequencing techniques, which have evolved from the analysis of a few hundred cells to the analysis of thousands of cells simultaneously, the study of tumor heterogeneity now becomes possible. Different modalities can be explored at the single-cell level: DNA, RNA, epigenetic modifications, and intracellular and cell surface proteins. In this review, we describe these techniques and highlight their advantages and limitations in the study of ALL biology. Moreover, multiomics technologies and the incorporation of the spatial dimension can provide insight into intercellular communication. We describe how the different single-cell sequencing technologies help to unravel the molecular complexity of ALL, shedding light on its development, its heterogeneity, its interaction with the leukemia microenvironment and possible relapse mechanisms.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"727-744"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study.","authors":"Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang","doi":"10.1007/s40291-024-00736-8","DOIUrl":"10.1007/s40291-024-00736-8","url":null,"abstract":"<p><strong>Introduction: </strong>Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping.</p><p><strong>Methods: </strong>We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA.</p><p><strong>Results: </strong>Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months.</p><p><strong>Conclusions: </strong>Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"803-810"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis from a Diagnostic Perspective: 10 Years of CHIP.","authors":"Lasse Kjær, Vibe Skov, Morten Kranker Larsen, Marie Hvelplund Kristiansen, Troels Wienecke, Sabrina Cordua, Christina Ellervik, Stephen E Langabeer, Hans Carl Hasselbalch","doi":"10.1007/s40291-024-00737-7","DOIUrl":"10.1007/s40291-024-00737-7","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"665-668"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Afamitresgene Autoleucel: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40291-024-00749-3","DOIUrl":"10.1007/s40291-024-00749-3","url":null,"abstract":"<p><p>Afamitresgene autoleucel (TECELRA^®), a genetically modified human leukocyte antigen (HLA)-restricted autologous melanoma-associated antigen 4 (MAGE-A4)-directed T cell immunotherapy, is being developed by Adaptimmune Therapeutics plc, for the treatment of solid tumours expressing the MAGE-A4 antigen. In August 2024, afamitresgene autoleucel was approved in the USA under accelerated approval for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P or -A*02:06P positive and whose tumour expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. This article summarizes the milestones in the development of afamitresgene autoleucel leading to this first approval for the treatment of advanced synovial sarcoma.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"861-866"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of a Rapid Digital PCR Test for the Detection of Non-Small Cell Lung Cancer (NSCLC) Variants.","authors":"Abdulaziz F Al Mana, Kristen Culp, Abby Keeler, Orlando Perrera, Malini Rajagopalan, Lucien Jacky, Brad Brown, Bharat Thyagarajan","doi":"10.1007/s40291-024-00732-y","DOIUrl":"10.1007/s40291-024-00732-y","url":null,"abstract":"<p><strong>Background: </strong>Next-generation sequencing is widely used for comprehensive molecular profiling for many cancers including lung cancer. However, the complex workflows and long turnaround times limit its access and utility. ChromaCode's High Definition PCR Non-Small Cell Lung Cancer Panel (HDPCR™ NSCLC Panel) is a low-cost, rapid turnaround, digital polymerase chain reaction assay that is designed to detect variants in nine NSCLC genes listed in National Comprehensive Cancer Network guidelines.</p><p><strong>Methods: </strong>This assay uses TaqMan^® probe limiting chemistry and proprietary analysis software to enable multi-target detection within a single-color channel. We compared the performance of the HDPCR™ NSCLC Panel against an in-house, laboratory-developed, targeted next-generation sequencing panel used in the Molecular Diagnostics Laboratory at the University of Minnesota Medical Center to detect biomarkers for NSCLC.</p><p><strong>Results: </strong>The overall accuracy of the HDPCR panel was 99.48% (95% confidence interval 99.01-99.76) with a sensitivity of 95.35% (95% confidence interval 88.52-98.72) and a specificity of 99.69% (95% confidence interval 99.29-99.90). The HDPCR wet lab workflow was 4 h, and the time to generate variant calls from raw data using the ChromaCode Cloud was 2 minutes.</p><p><strong>Conclusions: </strong>We demonstrated that the HDPCR™ NSCLC Panel provides timely, comprehensive, and sensitive mutation detection in NSCLC samples with results in less than 24 h.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"791-802"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterium tuberculosis Detection Using CRISPR Technology: An Updated Systematic Review and Meta-analysis.","authors":"Mohammad Abavisani, Sobhan Karbas Foroushan, Reza Khayami, Amirhossein Sahebkar","doi":"10.1007/s40291-024-00741-x","DOIUrl":"10.1007/s40291-024-00741-x","url":null,"abstract":"<p><strong>Background: </strong>Rapid and precise detection of Mycobacterium tuberculosis (MTB) is paramount for effective management and control of tuberculosis. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has emerged as a promising tool for pathogenic diagnosis owing to its specificity and adaptability. This systematic review and meta-analysis aimed to appraise the diagnostic accuracy of CRISPR-based techniques in identifying MTB.</p><p><strong>Methods: </strong>A meticulous search was conducted in Medline, Scopus, Embase, and ISI Web of Science to retrieve relevant studies, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality was assessed using the Joanna Briggs Institute checklist. Data synthesis and analyses, including subgroup analyses, were performed with R v 4.3.1, examining variables like CRISPR variants, gene targets, pre-amplification techniques, and signal readout methods.</p><p><strong>Results: </strong>From 389 identified studies, 14 met the inclusion criteria, encompassing 2175 MTB strains. The pooled sensitivity and specificity of CRISPR-based techniques were 0.93 (95% CI 0.85-0.99) and 0.97 (95% CI 0.94-0.99), respectively. The pooled diagnostic odds ratio was 273.4379 (95% CI 103.3311-723.5794), with an area under the curve of 0.97 for the summary receiver operating characteristic (SROC) curve, denoting excellent diagnostic accuracy. Subgroup analyses illustrated variations in diagnostic metrics based on factors like CRISPR variant utilized, target gene, and pre-amplification methods. For instance, CRISPR-Cas12 exhibited a sensitivity and specificity of 0.93 (95% CI 0.78-0.98) and 0.98 (95% CI 0.93-1), respectively. Moreover, this technology showed a sensitivity of 96% and specificity of 100% in detecting resistant MTB.</p><p><strong>Conclusion: </strong>CRISPR-based methods exhibit substantial diagnostic sensitivity and specificity for detecting MTB, with notable variances across different CRISPR variants and methodological approaches. Further studies must be conducted to optimize CRISPR's potential as a diagnostic tool for MTB in a variety of clinical and research settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"777-790"},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}