Radiogenomics

放射基因组学
  • 文章类型: Journal Article
    背景:三阴性乳腺癌(TNBC)是高度异质性的,导致患者对新辅助化疗(NAC)的反应和预后不同。这项研究旨在表征MRI上TNBC的异质性,并开发一种放射基因组模型来预测病理完全反应(pCR)和预后。
    方法:在这项回顾性研究中,在复旦大学上海肿瘤中心接受新辅助化疗的TNBC患者作为影像学发展队列(n=315);在这些患者中,可获得遗传数据的患者被纳入放射基因组发展队列(n=98).将两个队列的研究群体以7:3的比例随机分为训练集和验证集。外部验证队列(n=77)包括来自DUKE和I-SPY1数据库的患者。使用肿瘤内亚区域和肿瘤周围区域的特征来表征空间异质性。血流动力学异质性的特征在于来自肿瘤体的动力学特征。在选择特征后,通过逻辑回归建立了三个影像组学模型。模型1包括次区域和肿瘤周围特征,模型2包括动力学特征,模型3集成了模型1和模型2的功能。通过进一步整合病理和基因组特征来开发两个融合模型(PRM:病理学-放射组学模型;GPRM:基因组学-病理学-放射组学模型)。通过AUC和决策曲线分析评估模型性能。使用Kaplan-Meier曲线和多变量Cox回归评估预后影响。
    结果:在放射学模型中,代表多尺度异质性的多区域模型(模型3)表现出更好的pCR预测,训练中的AUC为0.87、0.79和0.78,内部验证,和外部验证集,分别。GPRM在训练(AUC=0.97,P=0.015)和验证集(AUC=0.93,P=0.019)中显示出预测pCR的最佳性能。模型3,PRM和GPRM可以通过无病生存期对患者进行分层,预测的非pCR与不良预后相关(P分别为0.034、0.001和0.019)。
    结论:DCE-MRI表征的多尺度异质性能有效预测TNBC患者的pCR和预后。放射基因组学模型可以作为有价值的生物标志物来提高预测性能。
    BACKGROUND: Triple-negative breast cancer (TNBC) is highly heterogeneous, resulting in different responses to neoadjuvant chemotherapy (NAC) and prognoses among patients. This study sought to characterize the heterogeneity of TNBC on MRI and develop a radiogenomic model for predicting both pathological complete response (pCR) and prognosis.
    METHODS: In this retrospective study, TNBC patients who underwent neoadjuvant chemotherapy at Fudan University Shanghai Cancer Center were enrolled as the radiomic development cohort (n = 315); among these patients, those whose genetic data were available were enrolled as the radiogenomic development cohort (n = 98). The study population of the two cohorts was randomly divided into a training set and a validation set at a ratio of 7:3. The external validation cohort (n = 77) included patients from the DUKE and I-SPY 1 databases. Spatial heterogeneity was characterized using features from the intratumoral subregions and peritumoral region. Hemodynamic heterogeneity was characterized by kinetic features from the tumor body. Three radiomics models were developed by logistic regression after selecting features. Model 1 included subregional and peritumoral features, Model 2 included kinetic features, and Model 3 integrated the features of Model 1 and Model 2. Two fusion models were developed by further integrating pathological and genomic features (PRM: pathology-radiomics model; GPRM: genomics-pathology-radiomics model). Model performance was assessed with the AUC and decision curve analysis. Prognostic implications were assessed with Kaplan‒Meier curves and multivariate Cox regression.
    RESULTS: Among the radiomic models, the multiregional model representing multiscale heterogeneity (Model 3) exhibited better pCR prediction, with AUCs of 0.87, 0.79, and 0.78 in the training, internal validation, and external validation sets, respectively. The GPRM showed the best performance for predicting pCR in the training (AUC = 0.97, P = 0.015) and validation sets (AUC = 0.93, P = 0.019). Model 3, PRM and GPRM could stratify patients by disease-free survival, and a predicted nonpCR was associated with poor prognosis (P = 0.034, 0.001 and 0.019, respectively).
    CONCLUSIONS: Multiscale heterogeneity characterized by DCE-MRI could effectively predict the pCR and prognosis of TNBC patients. The radiogenomic model could serve as a valuable biomarker to improve the prediction performance.
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  • 文章类型: Journal Article
    本研究旨在开发和验证放射基因组学列线图,用于在MRI和microRNAs(miRNA)的基础上预测肝细胞癌(HCC)中的微血管侵袭(MVI)。
    该队列研究包括168例经病理证实的HCC患者(训练队列:n=116;验证队列:n=52),他们接受了术前MRI和血浆miRNA检查。单变量和多变量逻辑回归用于确定与MVI相关的独立危险因素。这些风险因素用于产生列线图。通过受试者工作特征曲线(ROC)分析评估列线图的性能,灵敏度,特异性,准确度,和F1得分。进行决策曲线分析以确定列线图是否在临床上有用。
    MVI的独立危险因素是最大肿瘤长度,rad-score,和miRNA-21(均P<0.001)。敏感性,特异性,准确度,验证队列的列线图和F1评分分别为0.970,0.722,0.884和0.916.验证队列中的列线图的AUC为0.900(95%CI:0.808-0.992),高于任何其他单因素模型(最大肿瘤长度,rad-score,和miRNA-21)。
    放射基因组学列线图在预测HCC中的MVI方面显示出令人满意的预测性能,为肿瘤治疗决策提供了可行和实用的参考。
    UNASSIGNED: This study aimed to develop and validate a radiogenomics nomogram for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) on the basis of MRI and microRNAs (miRNAs).
    UNASSIGNED: This cohort study included 168 patients (training cohort: n = 116; validation cohort: n = 52) with pathologically confirmed HCC, who underwent preoperative MRI and plasma miRNA examination. Univariate and multivariate logistic regressions were used to identify independent risk factors associated with MVI. These risk factors were used to produce a nomogram. The performance of the nomogram was evaluated by receiver operating characteristic curve (ROC) analysis, sensitivity, specificity, accuracy, and F1-score. Decision curve analysis was performed to determine whether the nomogram was clinically useful.
    UNASSIGNED: The independent risk factors for MVI were maximum tumor length, rad-score, and miRNA-21 (all P < 0.001). The sensitivity, specificity, accuracy, and F1-score of the nomogram in the validation cohort were 0.970, 0.722, 0.884, and 0.916, respectively. The AUC of the nomogram was 0.900 (95% CI: 0.808-0.992) in the validation cohort, higher than that of any other single factor model (maximum tumor length, rad-score, and miRNA-21).
    UNASSIGNED: The radiogenomics nomogram shows satisfactory predictive performance in predicting MVI in HCC and provides a feasible and practical reference for tumor treatment decisions.
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  • 文章类型: Journal Article
    背景:放射基因组学是一种新兴的技术,它集成了基因组学和基于医学图像的放射组学,这被认为是实现精准医学的一种有希望的方法。
    目的:本研究的目的是定量分析研究现状,动态趋势,和使用文献计量学方法在放射基因组学领域的进化轨迹。
    方法:从WebofScienceCoreCollection检索到截至2023年发表的相关文献。使用Excel分析年度出版趋势。VOSviewer用于构建关键词共现网络以及国家和机构之间的合作网络。CiteSpace用于引用关键词突发分析和可视化参考时间线。
    结果:共纳入3237篇论文,并以纯文本格式导出。出版物的年度数量呈逐年增长的趋势。中国和美国在这一领域发表的论文最多,在美国被引用次数最多,在荷兰被引用次数最高。关键词突发分析表明,几个关键词,包括“大数据”,“磁共振波谱”,肾细胞癌,\"\"阶段,\"和\"替莫唑胺,“近年来经历了一次引文爆发。时间线视图表明,参考文献可以分为8个簇:低级别神经胶质瘤,肺癌组织学,肺腺癌,乳腺癌,放射性肺损伤,表皮生长因子受体突变,晚期放疗毒性,和人工智能。
    结论:放射基因组学领域越来越受到全世界研究人员的关注,美国和荷兰是最具影响力的国家。探索基于大数据的人工智能方法来预测肿瘤对各种治疗方法的反应是目前该领域的研究热点。
    BACKGROUND: Radiogenomics is an emerging technology that integrates genomics and medical image-based radiomics, which is considered a promising approach toward achieving precision medicine.
    OBJECTIVE: The aim of this study was to quantitatively analyze the research status, dynamic trends, and evolutionary trajectory in the radiogenomics field using bibliometric methods.
    METHODS: The relevant literature published up to 2023 was retrieved from the Web of Science Core Collection. Excel was used to analyze the annual publication trend. VOSviewer was used for constructing the keywords co-occurrence network and the collaboration networks among countries and institutions. CiteSpace was used for citation keywords burst analysis and visualizing the references timeline.
    RESULTS: A total of 3237 papers were included and exported in plain-text format. The annual number of publications showed an increasing annual trend. China and the United States have published the most papers in this field, with the highest number of citations in the United States and the highest average number per item in the Netherlands. Keywords burst analysis revealed that several keywords, including \"big data,\" \"magnetic resonance spectroscopy,\" \"renal cell carcinoma,\" \"stage,\" and \"temozolomide,\" experienced a citation burst in recent years. The timeline views demonstrated that the references can be categorized into 8 clusters: lower-grade glioma, lung cancer histology, lung adenocarcinoma, breast cancer, radiation-induced lung injury, epidermal growth factor receptor mutation, late radiotherapy toxicity, and artificial intelligence.
    CONCLUSIONS: The field of radiogenomics is attracting increasing attention from researchers worldwide, with the United States and the Netherlands being the most influential countries. Exploration of artificial intelligence methods based on big data to predict the response of tumors to various treatment methods represents a hot spot research topic in this field at present.
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  • 文章类型: Journal Article
    背景:神经胶质瘤的准确分类对于选择免疫治疗至关重要,MRI包含大量的影像学特征,可能提示一些预后相关信号。我们的目标是预测新的亚型的胶质瘤使用影像学特征和表征他们的生存,免疫,基因组谱和药物反应。
    方法:我们最初从CPTAC数据集中获得了36名患者的341张图像,用于开发深度学习模型。收集来自TCGA_GBM的111名患者的1812张图像和来自TCGA_LGG的53名患者的152张图像用于测试和验证。开发了一种基于MaskR-CNN的深度学习方法,用于识别胶质瘤患者的新亚型并比较其生存状态,免疫浸润模式,基因组特征,特定药物,和不同亚型的预测模型。
    结果:200例胶质瘤患者(平均年龄,33年±19[标准偏差])。用于识别肿瘤区域的深度学习模型的准确度在测试集中达到88.3%(98/111),在验证集中达到83%(44/53)。根据放射学特征将样本分为两个亚型,显示出不同的预后结果(风险比,2.70).根据免疫浸润分析结果,预后较差的亚型被定义为免疫沉默放射组学(ISR)亚型(n=43),另一种亚型是免疫激活的放射组学(IAR)亚型(n=53)。亚型特异性基因组特征将细胞系分为ISR细胞系(n=9)和对照细胞系(n=13)。并鉴定了八种ISR特异性药物,其中4个已通过OCTAD数据库验证.三个基于机器学习的分类器显示放射学和基因组共同特征更好地预测胶质瘤的放射学亚型。
    结论:这些发现提供了关于放射基因组如何识别预测预后的特定亚型的见解。非侵入性的免疫和药物敏感性。
    BACKGROUND: Accurate classification of gliomas is critical to the selection of immunotherapy, and MRI contains a large number of radiomic features that may suggest some prognostic relevant signals. We aim to predict new subtypes of gliomas using radiomic features and characterize their survival, immune, genomic profiles and drug response.
    METHODS: We initially obtained 341 images of 36 patients from the CPTAC dataset for the development of deep learning models. Further 1812 images of 111 patients from TCGA_GBM and 152 images of 53 patients from TCGA_LGG were collected for testing and validation. A deep learning method based on Mask R-CNN was developed to identify new subtypes of glioma patients and compared the survival status, immune infiltration patterns, genomic signatures, specific drugs, and predictive models of different subtypes.
    RESULTS: 200 glioma patients (mean age, 33 years ± 19 [standard deviation]) were enrolled. The accuracy of the deep learning model for identifying tumor regions achieved 88.3 % (98/111) in the test set and 83 % (44/53) in the validation set. The sample was divided into two subtypes based on radiomic features showed different prognostic outcomes (hazard ratio, 2.70). According to the results of the immune infiltration analysis, the subtype with a poorer prognosis was defined as the immunosilencing radiomic (ISR) subtype (n = 43), and the other subtype was the immunoactivated radiomic (IAR) subtype (n = 53). Subtype-specific genomic signatures distinguished celllines into ISR celllines (n = 9) and control celllines (n = 13), and identified eight ISR-specific drugs, four of which were validated by the OCTAD database. Three machine learning-based classifiers showed that radiomic and genomic co-features better predicted the radiomic subtypes of gliomas.
    CONCLUSIONS: These findings provide insights into how radiogenomic could identify specific subtypes that predict prognosis, immune and drug sensitivity in a non-invasive manner.
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  • 文章类型: Journal Article
    MYCN拷贝数类别与神经母细胞瘤(NB)的预后密切相关。因此,这项研究旨在评估18F-氟脱氧葡萄糖(18F-FDG)正电子发射断层扫描/计算机断层扫描(PET/CT)影像特征对NB中MYCN拷贝数的预测能力。
    对104例经病理证实的小儿NB患者进行回顾性分析。为了开发生物组学模型(B-model),结合了临床和生物学方面,PET/CT影像学特征,PET定量参数,保留了多变量逐步Logistic回归的显着特征。通过最小绝对收缩和选择运算符(LASSO)和单变量分析确定了重要的影像组学特征。根据PET和CT扫描获得的影像组学特征,建立了影像组学模型(R-model)。结合重要的生物组学和放射组学特征,建立了Multi-omics模型(M-model)。建立以上3个模型以区分MYCN野生型和MYCN增益和MYCN扩增(MNA)。进行校准曲线和受试者工作特性(ROC)曲线分析以验证预测性能。进行了事后分析,以比较构建的M模型是否可以区分MYCN增益和MNA。
    M模型在区分MYCN野生与MYCN增益和MNA方面表现出出色的预测性能,优于B模型和R模型[曲线下面积(AUC)0.83,95%置信区间(CI):0.74-0.92vs.0.81,95%CI:0.72-0.90和0.79,95%CI:0.69-0.89]。校准曲线表明M模型具有最高的可靠性。事后分析揭示了M模型在区分MYCN增益与MNA方面的巨大潜力(AUC0.95,95%CI:0.89-1)。
    基于生物组学和影像组学特征的M模型是区分患有NB的儿科患者中MYCN拷贝数类别的有效工具。
    UNASSIGNED: The MYCN copy number category is closely related to the prognosis of neuroblastoma (NB). Therefore, this study aimed to assess the predictive ability of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) radiomic features for MYCN copy number in NB.
    UNASSIGNED: A retrospective analysis was performed on 104 pediatric patients with NB that had been confirmed by pathology. To develop the Bio-omics model (B-model), which incorporated clinical and biological aspects, PET/CT radiographic features, PET quantitative parameters, and significant features with multivariable stepwise logistic regression were preserved. Important radiomics features were identified through least absolute shrinkage and selection operator (LASSO) and univariable analysis. On the basis of radiomics features obtained from PET and CT scans, the radiomics model (R-model) was developed. The significant bio-omics and radiomics features were combined to establish a Multi-omics model (M-model). The above 3 models were established to differentiate MYCN wild from MYCN gain and MYCN amplification (MNA). The calibration curve and receiver operating characteristic (ROC) curve analyses were performed to verify the prediction performance. Post hoc analysis was conducted to compare whether the constructed M-model can distinguish MYCN gain from MNA.
    UNASSIGNED: The M-model showed excellent predictive performance in differentiating MYCN wild from MYCN gain and MNA, which was better than that of the B-model and R-model [area under the curve (AUC) 0.83, 95% confidence interval (CI): 0.74-0.92 vs. 0.81, 95% CI: 0.72-0.90 and 0.79, 95% CI: 0.69-0.89]. The calibration curve showed that the M-model had the highest reliability. Post hoc analysis revealed the great potential of the M-model in differentiating MYCN gain from MNA (AUC 0.95, 95% CI: 0.89-1).
    UNASSIGNED: The M-model model based on bio-omics and radiomics features is an effective tool to distinguish MYCN copy number category in pediatric patients with NB.
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  • 文章类型: Journal Article
    目的:多种脂质代谢途径的改变与肾透明细胞癌(ccRCC)的发展和侵袭性有关。在这项研究中,我们的目标是开发一种基于脂质代谢相关基因(LMRGs)的新型放射基因组学特征,可以准确预测ccRCC患者的生存.
    方法:首先,使用327ccRCC筛选存活相关的LMRG并基于癌症基因组图谱(TCGA)数据库构建基因标签。然后,分析了182个ccRCC,以建立将LMRGs签名与癌症成像档案(TCIA)数据库中的放射学特征联系起来的放射学特征,包括增强的CT图像和转录组测序数据。最后,我们使用TCIA和湘雅三医院的这些患者验证了鉴定的放射基因组学特征的预后能力.
    结果:我们确定了LMRGs签名,由13个基因组成,可以有效区分低风险和高风险患者,并作为总生存期(OS)的独立可靠预测指标。放射性基因组学签名,由9个放射学特征组成,可以准确预测患者LMRGs特征(低风险或高风险)的表达水平。通过训练集和验证集(比率为7:3)的0.75和0.74的AUC值证明了该放射基因组学签名的预测性能。分别。多变量分析证明放射性基因组学特征是OS的独立危险因素(HR=4.98,95%CI:1.72-14.43,P=0.003)。
    结论:LMRGs放射性基因组学特征可作为一种新的预后预测因子。
    OBJECTIVE: Multiple lipid metabolism pathways alterations are associated with clear cell renal cell carcinoma (ccRCC) development and aggressiveness. In this study, we aim to develop a novel radiogenomics signature based on lipid metabolism-related genes (LMRGs) that may accurately predict ccRCC patients\' survival.
    METHODS: First, 327 ccRCC were used to screen survival-related LMRGs and construct a gene signature based on The Cancer Genome Atlas (TCGA) database. Then, 182 ccRCC were analyzed to establish radiogenomics signature linking LMRGs signature to radiomic features in The Cancer Imaging Archive (TCIA) database included enhanced CT images and transcriptome sequencing data. Lastly, we validated the prognostic power of the identified radiogenomics signature using these patients of TCIA and the Third Xiangya Hospital.
    RESULTS: We identified the LMRGs signature, consisting of 13 genes, which could efficiently discriminate between low-risk and high-risk patients and serve as an independent and reliable predictor of overall survival (OS). Radiogenomics signature, comprised of 9 radiomic features, was created and could accurately predict the expression level of LMRGs signature (low- or high-risk) for patients. The predictive performance of this radiogenomics signature was demonstrated through AUC values of 0.75 and 0.74 for the training and validation sets (at a ratio of 7:3), respectively. Radiogenomics signature was proven to be an independent risk factor for OS by multivariable analysis (HR = 4.98, 95 % CI:1.72-14.43, P = 0.003).
    CONCLUSIONS: The LMRGs radiogenomics signature could serve as a novel prognostic predictor.
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  • 文章类型: Journal Article
    胶质瘤表现出的特定遗传亚型导致不同的临床课程,并且需要涉及神经学家的多学科团队,癫痫学家,神经肿瘤学家和神经外科医生。目前,神经胶质瘤的诊断主要围绕初步的放射学发现和随后的明确的手术诊断(通过手术取样).放射组学和放射基因组学具有精确诊断和预测生存和治疗反应的潜力。通过形态学,纹理,和从MRI数据得出的功能特征,以及基因组数据。尽管他们的优势,它仍然缺乏不同研究小组之间的特征提取和分析方法的标准化过程,这使得外部验证不可行。放射组学和放射基因组学可用于更好地了解胶质瘤的基因组基础,如肿瘤空间异质性,治疗反应,分子分类和肿瘤微环境免疫浸润。这些新技术也被用来预测组织学特征,胶质瘤的分级甚至总体生存率。在这次审查中,阐明了放射组学和放射基因组学的工作流程,最近关于机器学习或人工智能在神经胶质瘤中的研究。
    The specific genetic subtypes that gliomas exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of gliomas pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). Radiomics and radiogenomics present a potential to precisely diagnose and predict survival and treatment responses, via morphological, textural, and functional features derived from MRI data, as well as genomic data. In spite of their advantages, it is still lacking standardized processes of feature extraction and analysis methodology among different research groups, which have made external validations infeasible. Radiomics and radiogenomics can be used to better understand the genomic basis of gliomas, such as tumor spatial heterogeneity, treatment response, molecular classifications and tumor microenvironment immune infiltration. These novel techniques have also been used to predict histological features, grade or even overall survival in gliomas. In this review, workflows of radiomics and radiogenomics are elucidated, with recent research on machine learning or artificial intelligence in glioma.
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  • 文章类型: Journal Article
    简介:胶质母细胞瘤是一种高度恶性的中枢神经系统肿瘤,世界卫生组织Ⅳ,胶质母细胞瘤是最常见的原发性恶性肿瘤,由于其自身的特殊性和复杂性,由于不同的分子亚型,不同的患者往往受益于目前的常规治疗方案,在精准医学的背景下,应用深度学习识别脑成像中肿瘤的显著特征,预后预测评估结合临床数据,最大限度地提高每位患者从治疗方案中获益,是一种非侵入性的可行方案.方法:我们对现有的关于深度学习在胶质母细胞瘤中的作用的文献进行了全面回顾,涵盖分子分类和诊断,预后评估。结果:基于各种磁共振成像序列的数据,遗传信息,和临床组合能够进行胶质母细胞瘤的非侵入性预测性肿瘤诊断,并评估总体生存率和治疗反应的准确性.对于图像,标准化的图像采集和数据提取技术可以有效地转化为临床实践的学习模型。然而,必须认识到,使用深度学习治疗胶质母细胞瘤的干预措施仍处于起步阶段,模型的鲁棒性受到挑战,由于目前胶质母细胞瘤样本总数不足以用于大规模实验方法,这直接关系到模型的应用难度。结论:与影像组学和浅层机器学习相比,深度学习可以更健壮,非侵入性,和有效的方法,随着临床医生为胶质母细胞瘤患者制定个性化医疗方案,提供更有价值的信息。
    Introduction: Glioblastoma is a highly malignant central nervous system tumor, World Health Organization Ⅳ, glioblastoma is the most common primary malignancy, due to its own specificity and complexity, different patients often benefit from the current conventional treatment regimen because of different molecular subtypes, in the context of precision medicine, the application of deep learning to identify the salient features of tumors on brain imaging, prognostic predictive assessment combined with clinical data to maximize the benefits of each patient from the treatment regimen is a non-invasive and feasible regimen. Methods: We conducted a comprehensive review of the existing literature on the role of deep learning in glioblastomas, covering molecular classification and diagnosis, prognosis assessment. Results: Data based on a variety of magnetic resonance imaging sequences, genetic information, and clinical combinations enable noninvasive predictive tumor diagnosis of glioblastoma and assess overall survival and treatment response accuracy. For images, standardized image acquisition and data extraction techniques can be effectively translated into learning models for clinical practice. However, it must be recognized that interventions in the treatment of glioblastoma using deep learning are still in their infancy, and the robustness of the model is challenged, as the current total number of glioblastoma samples is insufficient for large-scale experimental methods, which is directly related to the difficulty of application of the model. Conclusion: Compared to radiomics and shallow machine learning, deep learning can be a more robust, non-invasive, and effective approach, providing more valuable information as clinicians develop personalized medical protocols for glioblastoma patients.
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  • 文章类型: Observational Study
    背景:放化疗是局部晚期且不可切除的非小细胞肺癌(NSCLC)患者的关键治疗方法,由于放射性肺炎(RP)的发病率很高,因此尽早识别高危患者至关重要。内源性因素对RP的影响越来越受到重视。本研究旨在探讨基于计算机断层扫描(CT)的放射组学结合基因组学在分析不可切除的III期NSCLC中≥2级RP风险中的价值。
    方法:在这项回顾性多中心观察研究中,分析了100例接受放化疗治疗的不可切除的III期NSCLC患者。从放疗前的CT图像中提取整个肺的影像组学特征。使用最小绝对收缩和选择算子算法进行最佳特征选择,以计算预测等级≥2RP的Rad分数。从福尔马林固定的石蜡包埋的预处理活检组织中提取基因组DNA。进行了单变量和多变量逻辑回归分析,以确定RP模型开发的预测因子。接收器工作特征曲线下的面积用于评估模型的预测能力。使用DeLong检验对不同模型之间的曲线下面积值进行统计比较。校准曲线和决策曲线用于证明歧视性和临床获益比,分别。
    结果:Rad评分由9个放射学特征构建,以预测≥2级RP。多变量分析表明,组织学,Rad-score,XRCC1(rs25487)等位基因突变是与RP相关的独立高危因素。综合模型结合临床因素的曲线下面积,影像组学,和基因组学显著高于任何单一模型(0.827对0.594、0.738或0.641)。校准和决策曲线分析证实了列线图令人满意的临床可行性和实用性。
    结论:组织学,Rad-score,和XRCC1(rs25487)等位基因突变可以预测放化疗后局部晚期不可切除的NSCLC患者的≥2级RP,结合临床因素的综合模型,影像组学,和基因组学显示出最佳的预测功效。
    BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC.
    METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively.
    RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram.
    CONCLUSIONS: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.
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  • 文章类型: Journal Article
    全基因组CRISPR-Cas9敲除筛选已成为识别驱动肿瘤生长的关键基因的强大方法。这项研究的目的是使用CRISPR-Cas9筛选数据库探索与低级胶质瘤(LGG)特异性相关的吞噬作用调节因子(PR)。识别这些核心PR可能会导致新的治疗靶标,并为非侵入性放射基因组学方法评估LGG患者的预后和治疗反应铺平道路。我们选择了24个在LGG中过表达和致死的PR进行分析。已识别的PR亚型(PRsClusters,geneClusters,和PRs评分模型)有效预测LGG患者的临床结局。免疫应答标记,发现CTLA4等与PR评分显著相关.使用各种机器学习分类器构建了九个放射基因组学模型来揭示生存风险。测试和训练数据集中这些模型的曲线下面积(AUC)值分别为0.686和0.868。CRISPR-Cas9筛选鉴定了与LGG患者中特定PR相关基因的表达状态良好相关的新型预后放射基因组学生物标志物。这些生物标志物使用癌症基因组图谱(TCGA)数据库成功地对患者生存结果和治疗反应进行分层。这项研究对制定精确的临床治疗策略具有重要意义,并有望在未来为LGG患者提供更准确的治疗方法。
    Genome-wide CRISPR-Cas9 knockout screens have emerged as a powerful method for identifying key genes driving tumor growth. The aim of this study was to explore the phagocytosis regulators (PRs) specifically associated with lower-grade glioma (LGG) using the CRISPR-Cas9 screening database. Identifying these core PRs could lead to novel therapeutic targets and pave the way for a non-invasive radiogenomics approach to assess LGG patients\' prognosis and treatment response. We selected 24 PRs that were overexpressed and lethal in LGG for analysis. The identified PR subtypes (PRsClusters, geneClusters, and PRs-score models) effectively predicted clinical outcomes in LGG patients. Immune response markers, such as CTLA4, were found to be significantly associated with PR-score. Nine radiogenomics models using various machine learning classifiers were constructed to uncover survival risk. The area under the curve (AUC) values for these models in the test and training datasets were 0.686 and 0.868, respectively. The CRISPR-Cas9 screen identified novel prognostic radiogenomics biomarkers that correlated well with the expression status of specific PR-related genes in LGG patients. These biomarkers successfully stratified patient survival outcomes and treatment response using The Cancer Genome Atlas (TCGA) database. This study has important implications for the development of precise clinical treatment strategies and holds promise for more accurate therapeutic approaches for LGG patients in the future.
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