molecular typing

分子分型
  • 文章类型: Journal Article
    背景:本研究的目的是评估多参数超声成像组学模型在预测乳腺癌术后复发风险和分子分型方面的功效。
    方法:回顾性分析534例经术前超声和病理确诊为乳腺癌的女性患者。2018年1月至2023年6月在新疆医科大学附属肿瘤医院就诊。单因素分析和多因素logistic回归模型用于确定与临床特征相关的独立危险因素。PyRadiomics软件包用于在选定的超声图像中描绘感兴趣的区域并提取放射学特征。随后,通过最小绝对收缩和选择算子(LASSO)回归和支持向量机(SVM)方法建立影像学评分。使用受试者工作特征(ROC)曲线评估模型的预测性能,并计算曲线下面积(AUC)。通过校准曲线和判定曲线评价诊断效能和临床实用性。
    结果:在训练集中,术后复发风险预测模型的AUC值为0.9489,他们是0.8491。关于分子分型预测模型,HER-2过表达表型的训练集和验证集中的AUC值分别为0.93和0.92,TNBC表型为0.94和0.74,腔A表型为1.00和0.97,腔B表型为1.00和0.89,分别。在全面分析校准和判定曲线的基础上,结果表明,该模型具有较强的预测性能和临床实用性。
    结论:使用多参数超声成像组学在预测乳腺癌术后复发风险和分子分型方面具有重要价值。这种非侵入性方法为该病的诊断和治疗提供了至关重要的指导。
    BACKGROUND: The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer.
    METHODS: A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves.
    RESULTS: In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability.
    CONCLUSIONS: The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.
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  • 文章类型: Journal Article
    背景:已发现血管生成是发展肿瘤和缺血性疾病的关键因素。然而,血管生成相关基因(ARGs)在急性心肌梗死(AMI)中的作用尚不清楚.
    方法:使用GSE66360数据集作为训练组,GSE48060数据集用作外部验证队列。使用随机森林(RF)算法来鉴定特征基因。使用共有聚类分析来鉴定与血管生成相关的稳健分子簇。采用ssGSEA分析ARGs与免疫细胞浸润的相关性。此外,我们构建了miRNA基因,转录因子网络,和标记基因的靶向药物网络。RT-qPCR用于验证标记基因的表达水平。
    结果:根据RF算法确定了7个特征ARG。受试者工作特征曲线证实了基于特征ARG的风险预测模型的分类准确性(训练队列中曲线下面积[AUC]=0.9596,外部验证队列中AUC=0.7773)。随后,通过共识聚类确定ARG聚类.B簇具有更广泛的ARGs高表达,并且与免疫浸润显着相关。miRNA和转录因子网络为寻找潜在的上游靶标和生物标志物提供了新思路。最后,RT-qPCR结果与生物信息学分析结果一致,进一步验证我们的结果。
    结论:血管生成与AMI密切相关,和描述AMI患者的血管生成特征有助于对患者进行风险分层并提供个性化治疗。
    Angiogenesis has been discovered to be a critical factor in developing tumors and ischemic diseases. However, the role of angiogenesis-related genes (ARGs) in acute myocardial infarction (AMI) remains unclear.
    The GSE66360 dataset was used as the training cohort, and the GSE48060 dataset was used as the external validation cohort. The random forest (RF) algorithm was used to identify the signature genes. Consensus clustering analysis was used to identify robust molecular clusters associated with angiogenesis. The ssGSEA was used to analyze the correlation between ARGs and immune cell infiltration. In addition, we constructed miRNA-gene, transcription factor network, and targeted drug network of signature genes. RT-qPCR was used to verify the expression levels of signature genes.
    Seven signature ARGs were identified based on the RF algorithm. Receiver operating characteristic curves confirmed the classification accuracy of the risk predictive model based on signature ARGs (area under the curve [AUC] = 0.9596 in the training cohort and AUC = 0.7773 in the external validation cohort). Subsequently, the ARG clusters were identified by consensus clustering. Cluster B had a more generalized high expression of ARGs and was significantly associated with immune infiltration. The miRNA and transcription factor network provided new ideas for finding potential upstream targets and biomarkers. Finally, the results of RT-qPCR were consistent with the bioinformatics analysis, further validating our results.
    Angiogenesis is closely related to AMI, and characterizing the angiogenic features of patients with AMI can help to risk-stratify patients and provide personalized treatment.
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  • 文章类型: Journal Article
    背景:肝细胞癌(HCC)是一种非常普遍和致命的癌症,对晚期患者的治疗选择有限。二硫键凋亡是最近发现的程序性细胞死亡机制,由于葡萄糖饥饿诱导的细胞二硫键骨架的崩解,该机制发生在SLC7A11高表达细胞中。我们的目的是探索二硫化物沉积的潜力,作为肝癌的预后和治疗标志物。
    方法:我们使用非负矩阵分解(NMF)算法,根据31个双硫蛋白的转录谱,将HCC患者分为两种双硫蛋白亚型(C1和C2)。Further,通过Cox回归分析和机器学习算法筛选了5个基因(NEIL3,MMP1,STC2,ADH4和CFHR3),以构建二硫下垂评分系统(disulfisms)。细胞增殖试验,使用F-肌动蛋白染色和PBMC共培养模型来验证二硫化物下垂发生在HCC中并与免疫疗法反应相关。
    结果:我们的结果表明,低二硫上清液亚型(C2)表现出更好的总生存期(OS)和无进展生存期(PFS)预后,伴随着较低水平的免疫抑制细胞浸润和甘氨酸/丝氨酸/苏氨酸代谢途径的激活。此外,低二硫键下垂组显示出更好的免疫治疗反应和索拉非尼治疗的潜在拮抗作用.作为总生存风险因素,disurfS在多个验证队列中表现出很高的预测功效。我们证明了HCC细胞中二硫键的存在及其与免疫治疗致敏的可能相关性。
    结论:本研究表明,与二硫键凋亡相关的新型生物标志物可作为肝癌的有用临床诊断指标,能够预测预后和识别潜在的治疗目标。
    BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC.
    METHODS: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response.
    RESULTS: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization.
    CONCLUSIONS: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets.
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  • 文章类型: Journal Article
    在这项研究中,我们研究了分子分型联合正电子发射断层扫描(PET)/磁共振成像(MRI)半定量指标在子宫内膜癌危险分层中的价值.
    对86例经病理诊断为子宫内膜癌并在妇产科刮宫后接受手术治疗的患者进行了回顾性研究,宣武医院,2017年1月至2023年3月的首都医科大学。手术前,每位患者均接受了完整的PET/MRI检查.术后标本均行病理诊断,免疫组织化学,和POLE基因测序。四种分子亚型之间临床病理特征的差异以及整合的PET/MRI半定量指标的差异(SUVmax,分析四种分子亚型之间的ADCmin)。确定分子分型结合整合PET/MRI半定量指标对子宫内膜癌风险分层的临界值。
    子宫内膜癌4种分子亚型在病理类型和肿瘤分级上存在统计学差异。分子亚型的4个整合PET/MRI半定量指标(SUVmax和ADCmin)的值具有统计学差异。p53abn突变组SUVmax大于POLE突变组(P<0.05)。POLE突变组和MMR-d组的ADC最小值低于NSMP组(P<0.05)。分子分型结合PET/MRI半定量SUVmax指数可预测子宫内膜癌的低/中风险组及中-高/高风险组。SUVmax预测早期子宫内膜癌风险的临界值为14.72(敏感性为66.7%,特异性68.7%)。
    分子分型结合整合的PET/MRI半定量指标有助于对诊断为子宫内膜癌的患者实现风险分层并指导个体化治疗。
    UNASSIGNED: In this study, we investigated the value of molecular typing combined with integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) semi-quantitative indices in endometrial cancer risk stratification.
    UNASSIGNED: A retrospective study was conducted on 86 patients who were pathologically diagnosed with endometrial cancer and underwent surgical treatment after curettage at the Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University between January 2017 and March 2023. Prior to surgery, each patient underwent integrated PET/MRI examination. The postoperative samples were subjected to pathological diagnosis, immunohistochemistry, and POLE gene sequencing. The differences in clinicopathological features between the four molecular subtypes and the differences in integrated PET/MRI semi-quantitative indexes (SUV max, ADC min) between the four molecular subtypes were analyzed. The cutoff value of molecular typing combined with integrated PET/MRI semi-quantitative indices for endometrial cancer risk stratification was determined.
    UNASSIGNED: There were statistically significant differences in pathological types and tumor grades among the four molecular subtypes of endometrial cancer. The values of the four integrated PET/MRI semi-quantitative indices (SUV max and ADC min) of the molecular subtypes were statistically different. The SUV max was greater in the p53abn mutation group than in the POLE mutation group (P < 0.05). The ADC minimum of the POLE mutation group and the MMR-d group was lower than the NSMP group (P < 0.05). Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%).
    UNASSIGNED: Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.
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  • 文章类型: Journal Article
    本研究的目的是通过分子方法对耐碳青霉烯类鲍曼不动杆菌(CRAB)分离株进行分型,以调查世界各地的分子流行病学。需要多种分型技术来了解由鲍曼不动杆菌引起的暴发的来源和性质(A.鲍曼不动杆菌)和对抗生素的获得性抗性。如今,从传统的分型方法逐渐转向现代分子方法,以研究分子流行病学和感染控制。鲍曼不动杆菌菌株的分子分型在过去20年中发生了重大变革。一些基于测序的技术已经被证明是一个突破,并开辟了新的前景,这是传统方法无法实现的。在这次审查中,讨论了不同的预先存在和最近使用的分型方法,以探索鲍曼不动杆菌在人类感染背景下的分子流行病学。
    The aim of this study was to go through the molecular methods used for typing of carbapenem-resistant Acientobacter baumannii (CRAB) isolates for investigating the molecular epidemiology all over the world. Multiple typing techniques are required to understand the source and nature of outbreaks caused by Acientobacter baumannii (A. baumannii) and acquired resistance to antimicrobials. Nowadays, there is gradual shift from traditional typing methods to modern molecular methods to study molecular epidemiology and infection control. Molecular typing of A. baumannii strains has been revolutionized significantly in the last 2 decades. A few sequencing-based techniques have been proven as a breakthrough and opened new prospects, which have not been achieved by the traditional methods. In this review, discussed different pre-existing and recently used typing methods to explore the molecular epidemiology of A. baumannii pertaining in context with human infections.
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  • 文章类型: Journal Article
    高通量蛋白质组学分析技术的最新进展有助于同时对多个样本中的多种蛋白质进行精确定量。研究人员有机会全面分析大量医学标本或疾病模式细胞系中的分子特征。随着数据分析和集成的进步,蛋白质组学数据可以有效地巩固和利用,以识别精确的基本分子机制和解码个体生物标志物,指导肿瘤的精准治疗。在这里,我们回顾了广泛的蛋白质组学技术以及蛋白质组学数据整合的进展和方法,并进一步讨论了如何在精准医学和临床环境中更好地合并蛋白质组学。
    Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.
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  • 文章类型: Journal Article
    沙眼是世界范围内导致失明的主要传染病,现在主要局限于大约40个低收入和中等收入国家。它是由沙眼衣原体(Ct)引起的,一种具有传染性的胞内细菌.世界卫生组织建议使用阿奇霉素进行大规模药物治疗(MDA)以治疗和控制眼部Ct感染,同时改善面部清洁度和环境条件,以减少传播。了解沙眼的分子流行病学,特别是在MDA和传输动力学的背景下,Ct基因型的鉴定可能是有用的。虽然许多研究已经使用Ct主要外膜蛋白基因(ompA)进行基因分型,它有局限性。我们的研究将新型分型系统应用于沙眼,多基因座可变数量串联重复分析结合ompA(MLVA-ompA)。在2011年至2017年期间,从埃塞俄比亚的四个沙眼流行区收集MDA后的眼拭子。使用MLVA-ompA对300名具有高Ct聚合酶链反应(PCR)负荷的儿童的DNA进行分型,利用Ct基因组内的3个可变数量串联重复(VNTR)基因座。结果表明,MLVA-ompA显示出较高的判别力(0.981),超过了流行病学研究的推荐阈值。我们在26个地区确定了87个MLVA-ompA变体。在变异与临床体征或衣原体负荷之间没有发现显着关联。值得注意的是,在额外的MDA轮次后,整体Ct多样性显着下降,血清变型A后MDA的比例更高。尽管在对一个VNTR基因座(CT1299)进行测序方面存在挑战,MLVA-ompA显示出相对于全基因组测序的成本效益和效率。为沙眼防治计划提供有价值的当地流行病学信息。研究结果表明,MLVA-ompA可能是一种可靠的工具,用于键入眼Ct和理解传输动力学。协助制定有针对性的沙眼控制干预措施。
    Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission. To understand the molecular epidemiology of trachoma, especially in the context of MDA and transmission dynamics, the identification of Ct genotypes could be useful. While many studies have used the Ct major outer membrane protein gene (ompA) for genotyping, it has limitations. Our study applies a typing system novel to trachoma, Multiple Loci Variable Number Tandem Repeat Analysis combined with ompA (MLVA-ompA). Ocular swabs were collected post-MDA from four trachoma-endemic zones in Ethiopia between 2011-2017. DNA from 300 children with high Ct polymerase chain reaction (PCR) loads was typed using MLVA-ompA, utilizing 3 variable number tandem repeat (VNTR) loci within the Ct genome. Results show that MLVA-ompA exhibited high discriminatory power (0.981) surpassing the recommended threshold for epidemiological studies. We identified 87 MLVA-ompA variants across 26 districts. No significant associations were found between variants and clinical signs or chlamydial load. Notably, overall Ct diversity significantly decreased after additional MDA rounds, with a higher proportion of serovar A post-MDA. Despite challenges in sequencing one VNTR locus (CT1299), MLVA-ompA demonstrated cost-effectiveness and efficiency relative to whole genome sequencing, providing valuable information for trachoma control programs on local epidemiology. The findings suggest the potential of MLVA-ompA as a reliable tool for typing ocular Ct and understanding transmission dynamics, aiding in the development of targeted interventions for trachoma control.
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  • 文章类型: Journal Article
    布鲁氏菌病,主要由melitensis布鲁氏菌(B.melitensis),在中国被认为是一种重要的人畜共患疾病。在威海,位于山东半岛的东端,布鲁氏菌病在过去五年一直处于低流行阶段。
    这是过去五年布鲁氏菌病爆发的初步报告。B.melitensisbv菌株。3来自威海与其他城市表现出亲密的亲缘关系,暗示了一个潜在的共同祖先.
    流行病学调查依赖于公共卫生实验室的标准化和有效的分子分型方法和分析工具,以识别和追踪暴发。了解受灾严重地区自由放养家庭的牲畜流通模式对于控制布鲁氏菌病的传播至关重要。
    UNASSIGNED: Brucellosis, mainly caused by Brucella melitensis (B. melitensis), is regarded as a significant zoonotic disease in China. In Weihai, located at the eastern end of the Shandong Peninsula, brucellosis has been in a low epidemic phase for the past five years.
    UNASSIGNED: This was the initial report of a brucellosis outbreak in the last five years. Strains of B. melitensis bv. 3 from Weihai and other cities showed a close genetic relationship, suggesting a potential common ancestry.
    UNASSIGNED: Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace outbreaks. Understanding the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.
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  • 文章类型: Journal Article
    隐球菌病是世界范围内发生的主要危及生命的机会性/系统性真菌病之一,主要在免疫抑制患者中可以无症状或建立肺炎和脑膜脑炎,由新生隐球菌和C.gattii物种复合物引起。获取是通过从禽类粪便中吸入真菌繁殖体,树洞和腐烂的木材,以及分子类型与地理起源的关联,毒力和抗真菌耐药性具有流行病学重要性。由于Alagoas隐球菌病的数据有限,我们试图确定从临床和环境来源收集的病原体的分子类型.我们评估了先前从Maceió-Alagoas(巴西)的脑脊液和环境来源(鸽子粪便和树洞)收集的21种分离株。进行URA5基因的限制性片段长度多态性以在八种标准分子类型(VNI-VNIV和VGI-VGIV)中进行表征。在分离物中,66.67%(14)被分配给新生梭菌VNI-其中12个(12/14)从液体中回收,2个从树空洞中回收(2/14)。鸽子粪便中的一种分离物(4.76%)对应于新型梭菌VNIV,5株来自树洞,1株来自鸽子粪便(6株,28.57%)。VNI型存在于临床和环境样本中,并且在HIV阳性患者中观察到大多数新型梭菌感染。而VNIV和VGII型在阿拉戈斯州的环境来源中普遍存在。这是隐球菌属的第一个分子特征。在阿拉戈斯,我们的研究提供了有关隐球菌属生态流行病学的更多信息.在巴西,有助于更近距离地了解特有物种。
    Cryptococcosis is one of the major life-threatening opportunistic/systemic fungal diseases of worldwide occurrence, which can be asymptomatic or establish pneumonia and meningoencephalitis mainly in immunosuppressed patients, caused by the Cryptococcus neoformans and C. gattii species complexes. Acquisition is by inhaling fungal propagules from avian droppings, tree hollows and decaying wood, and the association of the molecular types with geographic origin, virulence and antifungal resistance have epidemiological importance. Since data on cryptococcosis in Alagoas are limited, we sought to determine the molecular types of etiological agents collected from clinical and environmental sources. We evaluated 21 isolates previously collected from cerebrospinal fluid and from environment sources (pigeon droppings and tree hollows) in Maceió-Alagoas (Brazil). Restriction fragment length polymorphism of URA5 gene was performed to characterize among the eight standard molecular types (VNI-VNIV and VGI-VGIV). Among isolates, 66.67% (14) were assigned to C. neoformans VNI - 12 of them (12/14) recovered from liquor and 2 from a tree hollow (2/14). One isolate from pigeon droppings (4.76%) corresponded to C. neoformans VNIV, while five strains from tree hollows and one from pigeon droppings (6, 28.57%) to C. gattii VGII. VNI-type was present in clinical and environmental samples and most C. neoformans infections were observed in HIV-positive patients, while types VNIV and VGII were prevalent in environmental sources in Alagoas. This is the first molecular characterization of Cryptococcus spp. in Alagoas, our study provides additional information on the ecoepidemiology of Cryptococcus spp. in Brazil, contributing to a closer view of the endemic species.
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  • 文章类型: Journal Article
    For more than 20 years gastrointestinal stromal tumors (GIST) have been a paradigm for a targeted treatment with tyrosine kinase inhibitors. A fundamental prerequisite for a neoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of a hereditary or syndromic predisposition must be considered because this results in consequences for the treatment and a different follow-up strategy.
    UNASSIGNED: Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei lokalisierten GIST bzw. eine additive Therapie bei metastasierten GIST ist die molekulare Typisierung der Tumoren, idealerweise bereits bei Erstdiagnose. Zudem ist auf die Möglichkeit einer hereditären oder syndromalen Prädisposition zu achten, da sich hieraus auch therapeutische Konsequenzen und eine andere Nachsorgestrategie ergeben.
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