Molecular tumour profiling by mass spectrometry (MS)

通过质谱 (MS) 进行分子肿瘤分析

• 批准号: 1790135
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1790135
• 关键词: Molecular; tumour; profiling; mass; spectrometry

The primary focus of this study will be investigation of molecular/mass spectral signatures associated with glioblastomas, a disease with a median survival rate of less than 15 months. The team will work with the clinical neuro-oncology team, accessing biopsy and resected tumour samples that have been imaged in vivo by PET and MR and ex vivo by immunohistochemistry and genetic profiling. Passages of these human-derived cell lines will be used to follow tumour evolution in preclinical xenograft models. The project therefore provides excellent multimodality data for comparison with the MS spectra and images.Collaborating with scientists at Waters (a University of Manchester strategic partner) will give access to both Desorption Electrospray Mass Spectrometry (DESI) and Rapid Evaporative Ionization Mass Spectrometry (REIMS) instrumentation. DESI and REIMS allow acquisition of mass spectra and MS images of tissues at ambient temperature, complementing other histopathological techniques. Our goal is to further develop tumour characterisation in terms of the heterogeneity of the tumour molecular/MS signature, through access to these new MS probe/imaging technologies, using multivariate statistical approaches to differentiate phenotypes within and between tumours, correlating the corresponding mass spectral signatures with data from the other imaging modalities and genetic profiles.We will test the hypothesis that MS interrogation of tumour samples can assist early diagnosis, surgical decision-making and the better understanding of mechanisms of disease progression. Outcomes will include a better understanding of tumour heterogeneity and evolution as well as the nature of the molecular signatures that characterise that heterogeneity or changes over time. We aim to better understand tissue spectra enhancing the capabilities of REIMS and DESI as tools for tumour staging, subtype identification and facilitate development of in situ probe technologies allowing tissue sampling in real-time during surgical procedures.Waters will also contribute in the form of a Case award.

本研究的主要重点是研究与胶质母细胞瘤相关的分子/质谱特征，胶质母细胞瘤是一种中位生存率低于15个月的疾病。该团队将与临床神经肿瘤学团队合作，通过PET和MR以及免疫组织化学和遗传分析进行活体成像，获取活检和切除的肿瘤样本。这些人源细胞系的传代将用于跟踪临床前异种移植模型中的肿瘤演变。因此，该项目提供了优秀的多模态数据，用于与MS光谱和图像进行比较。与沃茨（曼彻斯特大学的战略合作伙伴）的科学家合作，将提供解吸电喷雾质谱（DESI）和快速蒸发电离质谱（REIMS）仪器。DESI和REIMS允许在环境温度下采集组织的质谱和MS图像，补充其他组织病理学技术。我们的目标是通过使用这些新的MS探针/成像技术，使用多变量统计方法来区分肿瘤内和肿瘤之间的表型，将相应的质谱特征与来自其他成像方式和遗传特征的数据相关联。我们将测试肿瘤样本的MS询问可以有助于早期诊断、手术决策和更好地了解疾病进展机制。结果将包括更好地了解肿瘤的异质性和演变，以及表征异质性或随时间变化的分子特征的性质。我们的目标是更好地了解组织光谱，增强REIMS和DESI作为肿瘤分期、亚型识别工具的能力，并促进原位探针技术的开发，从而在手术过程中实现实时组织取样。沃茨还将以案例奖的形式做出贡献。