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Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: KRAS and beyond. 胰腺癌生物侵袭性和不良预后的基因组决定因素:KRAS 及其他
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-05-06 DOI: 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.

导言:胰腺癌具有明显的组织分子异质性。因此,在同一类肿瘤中,不同的肿瘤组织学具有不同的基因组特征:本专家综述以PubMed、SCOPUS和Embase(最后检索日期:2024年4月4日)中的数据为基础,介绍并讨论了胰腺癌生物侵袭性和不良预后的基本分子决定因素。首先,KRAS突变仍然是治疗胰腺癌最关键的难点之一。在该地区,超过 90% 的恶性肿瘤都存在 KRAS 突变。值得注意的是,KRAS突变的胰腺癌通常缺乏可用于分子疗法的可操作改变。此外,基于转录组的研究表明,鳞状表型的特点是预后和对标准化疗的反应较差。我们还讨论了与特定胰腺癌亚组预后不良有关的分子生物标志物,如标志环细胞癌中的 SMAD4 和导管内管状乳头状瘤浸润癌中的 TP53:专家意见:确定预后特别不良的胰腺癌亚组是开展具体研究工作的关键一步。除了实施和加强当前的精准肿瘤学策略外,改善胰腺癌患者生存率的决定性一步必须通过靶向 KRAS 基因来实现。
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引用次数: 0
Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies. 在 116,862 例妊娠中对胎儿性染色体非整倍体进行无创产前筛查的结果。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1080/14737159.2024.2333951
Yanfei Xu, Jianbo Lou, Yeqing Qian, Pengzhen Jin, Yangwen Qian, Jiawei Hong, Yuqing Xu, Yixuan Yin, Songjia Yi, Minyue Dong

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.

背景:无创产前筛查(NIPS)在筛查常见非整倍体方面表现良好。然而,它在检测胎儿性染色体非整倍体(SCA)方面的表现还需要在大规模的队列中进行评估:在这项回顾性观察中,共有116862名女性在2015年至2022年期间接受了基于DNA纳米球测序的NIPS。SCA根据核型或染色体微阵列分析(CMA)进行诊断。其中,2084 例单胎妊娠接受了核型分析和/或染色体微阵列分析。评估了NIPS对胎儿SCA的敏感性、特异性、阳性预测值(PPV)和阴性预测值(NPV):敏感性为 97.7%(95%CI,87.7-99.9),特异性为 87.3%(95%CI,76.5-94.4),阳性预测值为 96.1%(95%CI,86.5-99.5),阴性预测值为 95.7%(95%CI,78.1-99.9)。45,X、47,XXY、47,XXX 和 47,XYY 的 PPV 分别为 25.8%(95%CI,19.2-33.2)、80.9%(95%CI,69.5-89.4)、79.0%(95%CI,66.8-88.3)和 53.7%(95%CI,37.4-69.3)。45,X 的特异性为 94.1%(95%CI,93.0-95.1),性染色体三体(SCT)的特异性超过 99.0%。结论:结论:NIPS筛查胎儿SCA具有较高的灵敏度、特异性和NPV。结论:NIPS 筛查胎儿 SCA 的敏感性、特异性和 NPV 均较高,SCA 的 PPV 中等,但 45,X 的 PPV 低于 SCT。建议对高风险患者进行侵入性产前诊断。
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引用次数: 0
Association between NUDT17 polymorphisms and breast cancer risk. NUDT17 多态性与乳腺癌风险之间的关系。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-05-17 DOI: 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。
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引用次数: 0
Practical considerations for pathological diagnosis and molecular profiling of cholangiocarcinoma: an expert review for best practices. 胆管癌病理诊断和分子图谱分析的实用注意事项:最佳实践专家评论。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-05-16 DOI: 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。
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引用次数: 0
Sample-to-result molecular diagnostic platforms and their suitability for infectious disease testing in low- and middle-income countries. 样本到结果分子诊断平台及其对中低收入国家传染病检测的适用性。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-05-15 DOI: 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.

导言:诊断是医疗保健系统中不可或缺且价值被低估的一部分。对于许多疾病而言,分子诊断是黄金标准,但在中低收入国家(LMIC)却不容易实施。将所有程序整合到一个封闭系统中的样本到结果(S2R)平台可以提供一种解决方案。在本文中,我们研究了这些平台是否适合在中低收入国家实施:采用记分卡对不同平台的一系列参数进行评估。大多数平台在平台本身、易用性和检测耗材方面得分相当高;但也发现了成本、配送和针对低收入和中等收入国家需求的检测面板方面的不足。研究发现,高收入国家对常见传染病的诊断覆盖面要比低收入国家广。一项文献研究显示,在低收入和中等收入国家,这些平台主要用作诊断工具或评估诊断性能,只有少数平台评估操作特性或临床效用。在这篇叙述性综述中,我们提出了使 S2R 平台适应低收入和中等收入国家条件的各种要点:要使 S2R 平台适合在低收入与中等收入国家实施,可考虑由制造商进行一些修改。此外,加强卫生系统和数字化也至关重要;更小、更便宜、更快和可持续的技术也同样重要。
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引用次数: 0
Prognostic biomarkers in melanoma: a 2023 update from clinical trials in different therapeutic scenarios. 黑色素瘤的预后生物标志物:2023 年不同治疗方案临床试验的最新进展。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-05-13 DOI: 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.

简介在过去的十年中,黑色素瘤领域取得了重大进展,包括引入了新的分期系统,开发了免疫疗法和靶向疗法,从而改变了亚分期分类,影响了患者的预后。尽管取得了这些进展,但早期检测仍然至关重要。鉴于黑色素瘤的不可预测性,特别是在识别有复发风险的患者方面,对可靠的预后生物标志物的探索仍在继续。可靠的生物标志物对于做出明智的治疗决定至关重要:本综述全面回顾了免疫疗法和靶向疗法临床试验中的预后生物标志物。它探讨了不同的临床情况,包括辅助治疗、转移治疗和新辅助治疗。主要研究结果表明,肿瘤突变负荷、PD-L1表达、IFN-γ特征和免疫相关因素是有希望改善治疗反应的生物标志物:由于肿瘤的异质性,确定黑色素瘤治疗的实用预后因素具有挑战性。有希望的生物标志物包括肿瘤突变负荷(TMB)、循环肿瘤DNA以及肿瘤微环境特征,尤其是免疫成分。未来的研究应优先考虑大规模、前瞻性的研究,以验证这些生物标志物并使其标准化,同时强调临床相关性和实际应用性。易于获取的生物标志物有可能提高黑色素瘤治疗的精确性和有效性。
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引用次数: 0
Artificial Intelligence in Digital Histopathology for predicting patient prognosis and treatment efficacy in breast cancer. 数字组织病理学中的人工智能用于预测乳腺癌患者的预后和治疗效果。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-04-24 DOI: 10.1080/14737159.2024.2346545
William M. Gallagher, Christine McCaffrey, C. Jahangir, Clodagh Murphy, Caoimbhe Burke, Arman Rahman
INTRODUCTIONHistological images contain phenotypic information predictive of patient outcomes. Due to the heavy workload of pathologists, the time-consuming nature of quantitatively assessing histological features, and human eye limitations to recognize spatial patterns, manually extracting prognostic information in routine pathological workflows remains challenging. Digital pathology has facilitated the mining and quantification of these features utilizing whole-slide image (WSI) scanners and artificial intelligence (AI) algorithms. AI algorithms to identify image-based biomarkers from the tumor microenvironment (TME) have the potential to revolutionize the field of oncology, reducing delays between diagnosis and prognosis determination, allowing for rapid stratification of patients and prescription of optimal treatment regimes, thereby improving patient outcomes.AREAS COVEREDIn this review, the authors discuss how AI algorithms and digital pathology can predict breast cancer patient prognosis and treatment outcomes using image-based biomarkers, along with the challenges of adopting this technology in clinical settings.EXPERT OPINIONThe integration of AI and digital pathology presents significant potential for analyzing the TME and its diagnostic, prognostic, and predictive value in breast cancer patients. Widespread clinical adoption of AI faces ethical, regulatory, and technical challenges, although prospective trials may offer reassurance and promote uptake, ultimately improving patient outcomes by reducing diagnosis-to-prognosis delivery delays.
导言组织学图像包含可预测患者预后的表型信息。由于病理学家的工作量繁重、定量评估组织学特征耗时以及人眼识别空间模式的局限性,在常规病理工作流程中手动提取预后信息仍具有挑战性。数字病理学利用全切片图像(WSI)扫描仪和人工智能(AI)算法促进了对这些特征的挖掘和量化。从肿瘤微环境(TME)中识别基于图像的生物标记物的人工智能算法有可能彻底改变肿瘤学领域,减少诊断与预后判断之间的延迟,对患者进行快速分层并制定最佳治疗方案,从而改善患者的预后。在这篇综述中,作者讨论了人工智能算法和数字病理学如何利用基于图像的生物标志物来预测乳腺癌患者的预后和治疗效果,以及在临床环境中采用这项技术所面临的挑战。人工智能在临床上的广泛应用面临着伦理、监管和技术方面的挑战,不过前瞻性试验可以提供保证并促进其应用,最终通过减少诊断到预后的延迟来改善患者的预后。
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引用次数: 0
Clinical utilization of airway inflammatory biomarkers in the prediction and monitoring of clinical outcomes in patients with chronic obstructive pulmonary disease 气道炎症生物标志物在预测和监测慢性阻塞性肺病患者临床结果中的临床应用
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-04-18 DOI: 10.1080/14737159.2024.2344777
Dina Yehia, Clarus Leung, Don D. Sin
Chronic obstructive pulmonary disease (COPD) accounts for 545 million people living with chronic respiratory disorders and is the third leading cause of morbidity and mortality around the world. CO...
慢性阻塞性肺病 (COPD) 患者人数高达 5.45 亿,是全球发病率和死亡率的第三大原因。慢性阻塞性肺...
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引用次数: 0
The emerging role of liquid biopsy in oral squamous cell carcinoma detection: advantages and challenges 液体活检在口腔鳞状细胞癌检测中的新兴作用:优势与挑战
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-04-12 DOI: 10.1080/14737159.2024.2340997
Sudha Gupta, Brijesh Singh, Rajul Abhishek, Sameer Gupta, Manisha Sachan
Oral Squamous Cell Carcinoma (OSCC), the sixth most widespread malignancy in the world, accounts for 90% of all cases of oral cancer. The primary risk factors are tobacco chewing, alcohol consumpti...
口腔鳞状细胞癌(OSCC)是全球第六大最常见的恶性肿瘤,占所有口腔癌病例的 90%。主要的危险因素是咀嚼烟草、饮酒和吸烟。
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引用次数: 0
Tumor-infiltrating lymphocytes as a prognostic and predictive factor for Melanoma. 肿瘤浸润淋巴细胞是黑色素瘤的预后和预测因素。
IF 5.1 3区 医学 Q1 Medicine Pub Date : 2024-04-01 Epub Date: 2024-02-05 DOI: 10.1080/14737159.2024.2312102
Gracia Maria Vargas, Neha Shafique, Xiaowei Xu, Giorgos Karakousis

Introduction: Tumor-infiltrating lymphocytes (TILs) have been investigated as prognostic factors in melanoma. Recent advancements in assessing the tumor microenvironment in the setting of more widespread use of immune checkpoint blockade have reignited interest in identifying predictive biomarkers. This review examines the function and significance of TILs in cutaneous melanoma, evaluating their potential as prognostic and predictive markers.

Areas covered: A literature search was conducted on papers covering tumor infiltrating lymphocytes in cutaneous melanoma available online in PubMed and Web of Science from inception to 1 December 2023, supplemented by citation searching. This article encompasses the assessment of TILs, the role of TILs in the immune microenvironment, TILs as a prognostic factor, TILs as a predictive factor for immunotherapy response, and clinical applications of TILs in the treatment of cutaneous melanoma.

Expert opinion: Tumor-infiltrating lymphocytes play a heterogeneous role in cutaneous melanoma. While they have historically been associated with improved survival, their status as independent prognostic or predictive factors remains uncertain. Novel methods of TIL assessment, such as determination of TIL subtypes and molecular signaling, demonstrate potential for predicting therapeutic response. Further, while their clinical utility in risk-stratification in melanoma treatment shows promise, a lack of consensus data hinders standardized application.

简介:肿瘤浸润淋巴细胞(TILs肿瘤浸润淋巴细胞(TILs)是黑色素瘤的预后因素之一。最近,随着免疫检查点阻断技术的广泛应用,在评估肿瘤微环境方面取得的进展再次激发了人们对确定预测性生物标志物的兴趣。这篇综述探讨了TILs在皮肤黑色素瘤中的功能和意义,评估了它们作为预后和预测标志物的潜力:本文对PubMed和Web of Science上从开始到2023年12月1日期间有关皮肤黑色素瘤中肿瘤浸润淋巴细胞的在线文献进行了检索,并辅以引文检索。本文包括TILs的评估、TILs在免疫微环境中的作用、TILs作为预后因素、TILs作为免疫疗法反应的预测因素以及TILs在皮肤黑色素瘤治疗中的临床应用:肿瘤浸润淋巴细胞在皮肤黑色素瘤中发挥着不同的作用。虽然肿瘤浸润淋巴细胞历来与生存率的提高有关,但其作为独立预后或预测因素的地位仍不确定。新的 TIL 评估方法(如确定 TIL 亚型和分子信号转导)显示了预测治疗反应的潜力。此外,虽然它们在黑色素瘤治疗风险分级中的临床应用前景看好,但缺乏共识数据阻碍了它们的标准化应用。
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引用次数: 0
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Expert Review of Molecular Diagnostics
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