Molecular tumour profiling by mass spectrometry (MS)

这项研究的主要焦点将是研究与胶质母细胞瘤相关的分子/质量谱特征，这是一种中位存活率不到15个月的疾病。该团队将与临床神经肿瘤学团队合作，获取活体和切除的肿瘤样本，这些样本已经通过PET和MR在体内成像，并通过免疫组织化学和遗传图谱在体外进行成像。这些人类来源的细胞系的传代将用于在临床前异种移植模型中跟踪肿瘤的演变。与Waters(曼彻斯特大学的战略合作伙伴)的科学家合作，将获得解吸电喷雾质谱仪(DESI)和快速蒸发电离质谱仪(REIMS)仪器。DESI和REMS允许在环境温度下获取组织的质谱图和MS图像，作为其他组织病理学技术的补充。我们的目标是通过获得这些新的MS探针/成像技术，利用多变量统计方法来区分肿瘤内部和肿瘤之间的表型，将相应的质谱图特征与来自其他成像方式和遗传特征的数据相关联，进一步根据肿瘤分子/MS信号的异质性来进一步研究肿瘤的特征。我们将检验MS询问肿瘤样本可以帮助早期诊断、手术决策和更好地了解疾病进展机制的假设。结果将包括更好地了解肿瘤的异质性和进化，以及表征这种异质性或随时间变化的分子签名的性质。我们的目标是更好地了解组织光谱，增强REIM和DESI作为肿瘤分期、亚型识别工具的能力，并促进原位探测技术的开发，使其能够在手术过程中实时采集组织样本。Waters还将以案例奖励的形式做出贡献。

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.