Background: Malaria elimination mandates early and accurate diagnosis of infection. Although malaria diagnosis is programmatically dependent on microscopy/RDTs, molecular diagnosis has much better diagnostic accuracy. Higher cost of molecular diagnoses is a recognized challenge for use at the point of care. Because funding is always a recognized constraint, we performed financial cost-analyses of available molecular platforms for better utilization of available budget.
Methods: Two strategies were applied to deduce the cost per sample. Strategy 1 included recurring components (RC) in minimum pack size, and biologist's time whereas strategy 2 included only RC and non-recurring components and costs are calculated for sample sizes (1-1,000,000) to infer the sample size effect.
Results: Spin column-based manual DNA extraction (US$ 3.93 per sample) is the lowest-cost method, followed by magnetic bead-based automated, semi-automated, and PCI-based manual method. Further, DNA extraction cost per sample via spin column-based manual method and semi-automated method decreases with an increase in sample size up to 10,000. Real-time PCRs are ~ 2-fold more economical than conventional PCR, regardless of sample size.
Conclusions: This study is the first for malaria to estimate systematic molecular diagnosis financial costs. Kit-based and automated methods may replace conventional DNA extraction and amplification methods for a frugal high-throughput diagnosis.
背景:消除疟疾要求对感染进行早期准确诊断。尽管疟疾诊断在程序上依赖于显微镜/RDT,但分子诊断的诊断准确性要高得多。分子诊断的成本较高,这对在医疗点使用分子诊断是一个公认的挑战。由于资金始终是公认的制约因素,我们对现有的分子平台进行了财务成本分析,以便更好地利用现有预算:方法:我们采用了两种策略来推算每个样本的成本。方法:采用两种策略推算每个样本的成本。策略 1 包括最小包装中的经常性成本(RC)和生物学家的时间,而策略 2 仅包括经常性成本和非经常性成本,并计算样本量(1-1,000,000)的成本,以推断样本量效应:结果:基于旋转柱的手动 DNA 提取(每个样本 3.93 美元)是成本最低的方法,其次是基于磁珠的自动、半自动和基于 PCI 的手动方法。此外,通过旋柱式手动方法和半自动方法提取每个样本的 DNA 成本随着样本量的增加而降低,最高可达 10,000 个样本。无论样本量多少,实时 PCR 都比传统 PCR 经济约 2 倍:这项研究首次对疟疾的系统分子诊断成本进行了估算。基于试剂盒的自动方法可取代传统的 DNA 提取和扩增方法,从而实现节俭的高通量诊断。
{"title":"Cost analyses for malaria molecular diagnosis for research planners in India and beyond.","authors":"Vandana Panwar, Shivani Bansal, Charu Chauhan, Abhinav Sinha","doi":"10.1080/14737159.2024.2356172","DOIUrl":"10.1080/14737159.2024.2356172","url":null,"abstract":"<p><strong>Background: </strong>Malaria elimination mandates early and accurate diagnosis of infection. Although malaria diagnosis is programmatically dependent on microscopy/RDTs, molecular diagnosis has much better diagnostic accuracy. Higher cost of molecular diagnoses is a recognized challenge for use at the point of care. Because funding is always a recognized constraint, we performed financial cost-analyses of available molecular platforms for better utilization of available budget.</p><p><strong>Methods: </strong>Two strategies were applied to deduce the cost per sample. Strategy 1 included recurring components (RC) in minimum pack size, and biologist's time whereas strategy 2 included only RC and non-recurring components and costs are calculated for sample sizes (1-1,000,000) to infer the sample size effect.</p><p><strong>Results: </strong>Spin column-based manual DNA extraction (US$ 3.93 per sample) is the lowest-cost method, followed by magnetic bead-based automated, semi-automated, and PCI-based manual method. Further, DNA extraction cost per sample via spin column-based manual method and semi-automated method decreases with an increase in sample size up to 10,000. Real-time PCRs are ~ 2-fold more economical than conventional PCR, regardless of sample size.</p><p><strong>Conclusions: </strong>This study is the first for malaria to estimate systematic molecular diagnosis financial costs. Kit-based and automated methods may replace conventional DNA extraction and amplification methods for a frugal high-throughput diagnosis.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"549-559"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070531","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}
Pub Date : 2024-06-01Epub Date: 2024-06-17DOI: 10.1080/14737159.2024.2367466
Matheus Braga, Mariana Akemi Sonoda Shiga, Pedro Emanuel Santiago Silva, Aléia Harumi Uchibaba Yamanaka, Victor Hugo Souza, Sergio Grava, Andréa Name Colado Simão, Janisleya Silva Ferreira Neves, Quirino Alves de Lima Neto, Joana Maira Valentini Zacarias, Jeane Eliete Laguila Visentainer
Background: A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response.
Objective: The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in TLR3; rs2292151 in TICAM1; rs1758566 in IFNA1; rs1800629 in TNF, and rs1800795 in IL6 with the severity of Covid-19.
Methods: A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form.
Results: The T/T genotype of TLR3 in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of TICAM1 in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of IFNA1 in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19.
Conclusion: We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.
{"title":"Association between polymorphisms in <i>TLR3</i>, <i>TICAM1</i> and <i>IFNA1</i> genes and covid-19 severity in Southern Brazil.","authors":"Matheus Braga, Mariana Akemi Sonoda Shiga, Pedro Emanuel Santiago Silva, Aléia Harumi Uchibaba Yamanaka, Victor Hugo Souza, Sergio Grava, Andréa Name Colado Simão, Janisleya Silva Ferreira Neves, Quirino Alves de Lima Neto, Joana Maira Valentini Zacarias, Jeane Eliete Laguila Visentainer","doi":"10.1080/14737159.2024.2367466","DOIUrl":"10.1080/14737159.2024.2367466","url":null,"abstract":"<p><strong>Background: </strong>A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response.</p><p><strong>Objective: </strong>The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in <i>TLR3</i>; rs2292151 in <i>TICAM1</i>; rs1758566 in <i>IFNA1</i>; rs1800629 in <i>TNF</i>, and rs1800795 in <i>IL6</i> with the severity of Covid-19.</p><p><strong>Methods: </strong>A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form.</p><p><strong>Results: </strong>The T/T genotype of <i>TLR3</i> in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of <i>TICAM1</i> in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of <i>IFNA1</i> in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19.</p><p><strong>Conclusion: </strong>We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"525-531"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305790","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}
Pub Date : 2024-06-01Epub Date: 2024-07-08DOI: 10.1080/14737159.2024.2375233
Alexis F Wilkinson, Maria J Barra, Emilie N Novak, Meaghan Bond, Rebecca Richards-Kortum
Introduction: Suitable sample collection and preparation methods are essential to enable nucleic acid amplification testing at the point of care (POC). Strategies that allow direct isothermal nucleic acid amplification testing (iNAAT) of crude sample lysate without the need for nucleic acid extraction minimize time to result as well as the need for operator expertise and costly infrastructure.
Areas covered: The authors review research to understand how sample matrix and preparation affect the design and performance of POC iNAATs. They focus on approaches where samples are directly combined with liquid reagents for preparation and amplification via iNAAT strategies. They review factors related to the type and method of sample collection, storage buffers, and lysis strategies. Finally, they discuss RNA targets and relevant regulatory considerations.
Expert opinion: Limitations in sample preparation methods are a significant technical barrier preventing implementation of nucleic acid testing at the POC. The authors propose a framework for co-designing sample preparation and amplification steps for optimal performance with an extraction-free paradigm by considering a sample matrix and lytic strategy prior to an amplification assay and readout. In the next 5 years, the authors anticipate increasing priority on the co-design of sample preparation and iNAATs.
{"title":"Point-of-care isothermal nucleic acid amplification tests: progress and bottlenecks for extraction-free sample collection and preparation.","authors":"Alexis F Wilkinson, Maria J Barra, Emilie N Novak, Meaghan Bond, Rebecca Richards-Kortum","doi":"10.1080/14737159.2024.2375233","DOIUrl":"10.1080/14737159.2024.2375233","url":null,"abstract":"<p><strong>Introduction: </strong>Suitable sample collection and preparation methods are essential to enable nucleic acid amplification testing at the point of care (POC). Strategies that allow direct isothermal nucleic acid amplification testing (iNAAT) of crude sample lysate without the need for nucleic acid extraction minimize time to result as well as the need for operator expertise and costly infrastructure.</p><p><strong>Areas covered: </strong>The authors review research to understand how sample matrix and preparation affect the design and performance of POC iNAATs. They focus on approaches where samples are directly combined with liquid reagents for preparation and amplification via iNAAT strategies. They review factors related to the type and method of sample collection, storage buffers, and lysis strategies. Finally, they discuss RNA targets and relevant regulatory considerations.</p><p><strong>Expert opinion: </strong>Limitations in sample preparation methods are a significant technical barrier preventing implementation of nucleic acid testing at the POC. The authors propose a framework for co-designing sample preparation and amplification steps for optimal performance with an extraction-free paradigm by considering a sample matrix and lytic strategy prior to an amplification assay and readout. In the next 5 years, the authors anticipate increasing priority on the co-design of sample preparation and iNAATs.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"509-524"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554492","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}
Pub Date : 2024-05-01Epub Date: 2024-05-11DOI: 10.1080/14737159.2024.2351465
Mingze Guan, Hua Zhao, Qi Zhang, Li Li, Xiaobo Wang, Bo Tang
Background: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL).
Methods: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay.
Results: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL.
Conclusion: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.
{"title":"A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.","authors":"Mingze Guan, Hua Zhao, Qi Zhang, Li Li, Xiaobo Wang, Bo Tang","doi":"10.1080/14737159.2024.2351465","DOIUrl":"10.1080/14737159.2024.2351465","url":null,"abstract":"<p><strong>Background: </strong>Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL).</p><p><strong>Methods: </strong>We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay.</p><p><strong>Results: </strong>The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL.</p><p><strong>Conclusion: </strong>The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"439-457"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852498","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}
Pub Date : 2024-05-01Epub Date: 2024-05-06DOI: 10.1080/14737159.2024.2348676
Calogero Ciulla, Claudio Luchini
Introduction: A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.
Areas covered: Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, KRAS mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in KRAS-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as SMAD4 in signet-ring cell carcinoma and TP53 in invasive cancers derived from intraductal tubulopapillary neoplasms.
Expert opinion: The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the KRAS gene.
{"title":"Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: <i>KRAS</i> and beyond.","authors":"Calogero Ciulla, Claudio Luchini","doi":"10.1080/14737159.2024.2348676","DOIUrl":"10.1080/14737159.2024.2348676","url":null,"abstract":"<p><strong>Introduction: </strong>A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.</p><p><strong>Areas covered: </strong>Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, <i>KRAS</i> mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in <i>KRAS</i>-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as <i>SMAD4</i> in signet-ring cell carcinoma and <i>TP53</i> in invasive cancers derived from intraductal tubulopapillary neoplasms.</p><p><strong>Expert opinion: </strong>The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the <i>KRAS</i> gene.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"355-362"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861703","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}
Background: Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.
Research design and methods: In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated.
Results: The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all.
Conclusions: NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.
{"title":"Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies.","authors":"Yanfei Xu, Jianbo Lou, Yeqing Qian, Pengzhen Jin, Yangwen Qian, Jiawei Hong, Yuqing Xu, Yixuan Yin, Songjia Yi, Minyue Dong","doi":"10.1080/14737159.2024.2333951","DOIUrl":"10.1080/14737159.2024.2333951","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.</p><p><strong>Research design and methods: </strong>In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated.</p><p><strong>Results: </strong>The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all.</p><p><strong>Conclusions: </strong>NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"467-472"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206551","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}
Pub Date : 2024-05-01Epub Date: 2024-05-17DOI: 10.1080/14737159.2024.2353700
Junhui Han, Jing Liang, Wenqian Zhou, Man Zhang, Tianbo Jin
Background: Breast cancer (BC) is the leading cause of cancer death among women worldwide. The nudix hydrolase 17 (NUDT17) may play notable roles in cancer growth and metastasis. In this study, we explored the importance of NUDT17 gene polymorphism in patients with BC.
Methods: In our study, 563 BC patients and 552 healthy controls participated. We used logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI), and multifactor dimension reduction (MDR) analysis of SNP-SNP interactions. Finally, UALCAN and THPA databases were used for bioinformatics analysis.
Results: The rs9286836 G allele was associated with a decreased the BC risk (p = 0.022), and the carriers of rs2004659 G allele had a 32% decreased risk of BC than individuals with allele A (p = 0.004). In the four genetic models, rs9286836 and rs2004659 reduced the risk of BC. Additionally, we found that the NUDT17 SNPs were associated with BC risk under age, tumor size, and clinical stage stratification. The MDR analysis showed that the five-locus interaction model was the best in the multi-locus model.
Conclusion: Our study found that NUDT17 single nucleotide polymorphisms are associated with BC susceptibility in Chinese Han population.
背景:乳腺癌(BC)是全球女性癌症死亡的主要原因。nudix hydrolase 17(NUDT17)可能在癌症的生长和转移过程中发挥显著作用。本研究探讨了 NUDT17 基因多态性在 BC 患者中的重要性:在我们的研究中,有 563 名 BC 患者和 552 名健康对照者参与。我们使用逻辑回归分析计算几率比(OR)和95%置信区间(CI),并对SNP-SNP相互作用进行多因素降维(MDR)分析。最后,利用 UALCAN 和 THPA 数据库进行生物信息学分析:结果:rs9286836 G 等位基因与 BC 风险降低有关(p = 0.022),rs2004659 G 等位基因携带者的 BC 风险比等位基因 A 的个体降低 32%(p = 0.004)。在四个遗传模型中,rs9286836 和 rs2004659 可降低 BC 风险。此外,我们还发现,在年龄、肿瘤大小和临床分期分层的情况下,NUDT17 SNP 与 BC 风险相关。MDR分析表明,五病灶交互作用模型在多病灶模型中是最好的:我们的研究发现,NUDT17单核苷酸多态性与中国汉族人群的BC易感性有关。
{"title":"Association between <i>NUDT17</i> polymorphisms and breast cancer risk.","authors":"Junhui Han, Jing Liang, Wenqian Zhou, Man Zhang, Tianbo Jin","doi":"10.1080/14737159.2024.2353700","DOIUrl":"10.1080/14737159.2024.2353700","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the leading cause of cancer death among women worldwide. The nudix hydrolase 17 (NUDT17) may play notable roles in cancer growth and metastasis. In this study, we explored the importance of NUDT17 gene polymorphism in patients with BC.</p><p><strong>Methods: </strong>In our study, 563 BC patients and 552 healthy controls participated. We used logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI), and multifactor dimension reduction (MDR) analysis of SNP-SNP interactions. Finally, UALCAN and THPA databases were used for bioinformatics analysis.</p><p><strong>Results: </strong>The rs9286836 G allele was associated with a decreased the BC risk (<i>p</i> = 0.022), and the carriers of rs2004659 G allele had a 32% decreased risk of BC than individuals with allele A (<i>p</i> = 0.004). In the four genetic models, rs9286836 and rs2004659 reduced the risk of BC. Additionally, we found that the NUDT17 SNPs were associated with BC risk under age, tumor size, and clinical stage stratification. The MDR analysis showed that the five-locus interaction model was the best in the multi-locus model.</p><p><strong>Conclusion: </strong>Our study found that NUDT17 single nucleotide polymorphisms are associated with BC susceptibility in Chinese Han population.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"459-466"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956671","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}
Pub Date : 2024-05-01Epub Date: 2024-05-16DOI: 10.1080/14737159.2024.2353696
Matt Evans, Timothy Kendall
Introduction: Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity.
Areas covered: This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA.
Expert opinion: Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.
导言:精准医疗的进步扩大了靶向治疗的可及性,常规临床实践中对胆管癌(CCA)患者进行分子图谱分析的需求也随之增加。然而,病理学家在确定肝内 CCA(iCCA)明确诊断的同时又要保留足够的组织进行分子图谱分析时面临着挑战。此外,他们还经常面临如何以最佳方式处理组织以保持核酸完整性的挑战:本文首先指出了在病变肝活检中明确诊断 iCCA,同时保留足够的组织进行分子分析所面临的挑战。然后,作者探讨了分子图谱分析的临床价值、单基因和下一代测序 (NGS) 技术的基本原理以及基因组测试组织取样的挑战。他们还提出了一种用于 CCA 分子图谱分析的组织管理最佳实践算法:病理学家在组织取样和处理过程中面临着一些实际挑战。优化组织处理、谨慎组织处理以及选择合适的分子检测方法对于确保为尽可能多的病例提供最高质量的诊断信息至关重要。
{"title":"Practical considerations for pathological diagnosis and molecular profiling of cholangiocarcinoma: an expert review for best practices.","authors":"Matt Evans, Timothy Kendall","doi":"10.1080/14737159.2024.2353696","DOIUrl":"10.1080/14737159.2024.2353696","url":null,"abstract":"<p><strong>Introduction: </strong>Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity.</p><p><strong>Areas covered: </strong>This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA.</p><p><strong>Expert opinion: </strong>Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"393-408"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944435","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}
Pub Date : 2024-05-01Epub Date: 2024-05-15DOI: 10.1080/14737159.2024.2353690
Anne Hauner, Chukwuemeka Onwuchekwa, Kevin K Ariën
Introduction: Diagnostics are an essential, undervalued part of the health-care system. For many diseases, molecular diagnostics are the gold standard, but are not easy to implement in Low- and Middle-Income Countries (LMIC). Sample-to-result (S2R) platforms combining all procedures in a closed system could offer a solution. In this paper, we investigated their suitability for implementation in LMIC.
Areas covered: A scorecard was used to evaluate different platforms on a range of parameters. Most platforms scored fairly on the platform itself, ease-of-use and test consumables; however, shortcomings were identified in cost, distribution and test panels tailored to LMIC needs. The diagnostic coverage for common infectious diseases was found to have a wider coverage in high-income countries (HIC) than LMIC. A literature study showed that in LMIC, these platforms are mainly used as diagnostic tools or evaluation of diagnostic performance, with a minority assessing the operational characteristics or the clinical utility. In this narrative review, we identified various points for adaptation of S2R platforms to LMIC conditions.
Expert opinion: For S2R platforms to be suitable for implementation in LMIC some modifications by the manufacturers could be considered. Furthermore, strengthening health systems and digitalization are vital; as are smaller, cheaper, faster, and sustainable technologies.
{"title":"Sample-to-result molecular diagnostic platforms and their suitability for infectious disease testing in low- and middle-income countries.","authors":"Anne Hauner, Chukwuemeka Onwuchekwa, Kevin K Ariën","doi":"10.1080/14737159.2024.2353690","DOIUrl":"10.1080/14737159.2024.2353690","url":null,"abstract":"<p><strong>Introduction: </strong>Diagnostics are an essential, undervalued part of the health-care system. For many diseases, molecular diagnostics are the gold standard, but are not easy to implement in Low- and Middle-Income Countries (LMIC). Sample-to-result (S2R) platforms combining all procedures in a closed system could offer a solution. In this paper, we investigated their suitability for implementation in LMIC.</p><p><strong>Areas covered: </strong>A scorecard was used to evaluate different platforms on a range of parameters. Most platforms scored fairly on the platform itself, ease-of-use and test consumables; however, shortcomings were identified in cost, distribution and test panels tailored to LMIC needs. The diagnostic coverage for common infectious diseases was found to have a wider coverage in high-income countries (HIC) than LMIC. A literature study showed that in LMIC, these platforms are mainly used as diagnostic tools or evaluation of diagnostic performance, with a minority assessing the operational characteristics or the clinical utility. In this narrative review, we identified various points for adaptation of S2R platforms to LMIC conditions.</p><p><strong>Expert opinion: </strong>For S2R platforms to be suitable for implementation in LMIC some modifications by the manufacturers could be considered. Furthermore, strengthening health systems and digitalization are vital; as are smaller, cheaper, faster, and sustainable technologies.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"423-438"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921852","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}
Pub Date : 2024-05-01Epub Date: 2024-05-13DOI: 10.1080/14737159.2024.2347484
Gabriele Roccuzzo, Cristina Sarda, Valentina Pala, Simone Ribero, Pietro Quaglino
Introduction: Over the past decade, significant advancements in the field of melanoma have included the introduction of a new staging system and the development of immunotherapy and targeted therapies, leading to changes in substage classification and impacting patient prognosis. Despite these strides, early detection remains paramount. The quest for dependable prognostic biomarkers is ongoing, given melanoma's unpredictable nature, especially in identifying patients at risk of relapse. Reliable biomarkers are critical for informed treatment decisions.
Areas covered: This review offers a comprehensive review of prognostic biomarkers in the context of clinical trials for immunotherapy and targeted therapy. It explores different clinical scenarios, including adjuvant, metastatic, and neo-adjuvant settings. Key findings suggest that tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors are promising biomarkers associated with improved treatment responses.
Expert opinion: Identifying practical prognostic factors for melanoma therapy is challenging due to the tumor's heterogeneity. Promising biomarkers include tumor mutational burden (TMB), circulating tumor DNA, and those characterizing the tumor microenvironment, especially the immune component. Future research should prioritize large-scale, prospective studies to validate and standardize these biomarkers, emphasizing clinical relevance and real-world applicability. Easily accessible biomarkers have the potential to enhance the precision and effectiveness of melanoma management.
{"title":"Prognostic biomarkers in melanoma: a 2023 update from clinical trials in different therapeutic scenarios.","authors":"Gabriele Roccuzzo, Cristina Sarda, Valentina Pala, Simone Ribero, Pietro Quaglino","doi":"10.1080/14737159.2024.2347484","DOIUrl":"10.1080/14737159.2024.2347484","url":null,"abstract":"<p><strong>Introduction: </strong>Over the past decade, significant advancements in the field of melanoma have included the introduction of a new staging system and the development of immunotherapy and targeted therapies, leading to changes in substage classification and impacting patient prognosis. Despite these strides, early detection remains paramount. The quest for dependable prognostic biomarkers is ongoing, given melanoma's unpredictable nature, especially in identifying patients at risk of relapse. Reliable biomarkers are critical for informed treatment decisions.</p><p><strong>Areas covered: </strong>This review offers a comprehensive review of prognostic biomarkers in the context of clinical trials for immunotherapy and targeted therapy. It explores different clinical scenarios, including adjuvant, metastatic, and neo-adjuvant settings. Key findings suggest that tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors are promising biomarkers associated with improved treatment responses.</p><p><strong>Expert opinion: </strong>Identifying practical prognostic factors for melanoma therapy is challenging due to the tumor's heterogeneity. Promising biomarkers include tumor mutational burden (TMB), circulating tumor DNA, and those characterizing the tumor microenvironment, especially the immune component. Future research should prioritize large-scale, prospective studies to validate and standardize these biomarkers, emphasizing clinical relevance and real-world applicability. Easily accessible biomarkers have the potential to enhance the precision and effectiveness of melanoma management.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"379-392"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912088","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}