Charakterisierung der Raman-Signaturen von Epithelzellen in unterschiedlichen Stadien der malignen Transformation im Tiermodell der Adenom-Karzinom-Sequenz im Kolon

在本建议的上下文中，基于拉曼光谱的有效和快速的组织诊断的基础，应进一步评估的腺瘤-癌-序列的光谱建模，不同人群的拉曼诊断模型的影响和诊断模型对人类样本的可转移性。基于已经获得的拉曼数据的腺瘤-癌-序列的光谱建模进行了研究，以引出癌变过程中的光谱变化。基于该建模，可以确定腺瘤-癌序列期间的时间点，在该时间点可以基于拉曼特征进行可靠的诊断。此外，计划分别研究不同遗传倾向的动物。要回答的问题是，这些人群中的致癌作用是否不同，因此，基于拉曼光谱的诊断方法必须反映这些差异。这可以通过为两个群体构建拉曼诊断模型并通过随后比较这些模型的光谱轮廓和分类精度来进行测试。在这样做的时候，需要大量的两个种群的动物来得出可靠的统计结论。由于许多实验数据可以从第一个供资期使用，只有少数数据需要再次测量。本研究的第三个重点在于测试动物模型到人类样本的可转移性。在这种概念验证方法中，记录了人体样本（腺瘤、癌、正常粘膜）的拉曼光谱，以评价与小鼠组织切片测量结果的可比性。如果具有可比性，则可直接采用小鼠研究的结果/模型。如果不能保证可比性，则应首先进行测试以解开人类的拉曼癌症特征。所有这些研究的目标是更好地了解基于拉曼的癌症诊断，其潜力和局限性。

In the context of the present proposal the foundations for an efficient and rapid tissue diagnostics based on Raman spectroscopy should be further evaluated in terms of a spectroscopic modeling of the adenoma-carcinoma-sequence, the influence of different populations on a Raman-based diagnostic model and the transferability of diagnostic models on human samples. Based on the Raman data already obtained the spectroscopic modeling of the adenoma-carcinoma-sequence is investigated, in order to elicit the spectral changes during carcinogenesis. Based on this modeling the time point during the adenoma-carcinoma-sequence can be determined, at which a reliable diagnosis can be made based on the Raman signature. Furthermore, it is planned to separately study animals of different genetic dispositions. The question to be answered is whether the carcinogenesis differs in these populations and, consequently, a Raman-based diagnosis method must reflect these differences. This can be tested by constructing a Raman diagnostic model for the two populations and by comparing these models afterwards with respect to their spectral profile and their classification accuracies. In doing so, a large number of animals for both populations is needed to draw reliable statistical conclusions. Since many experimental data can be used from the first funding period, only a few data have to be measured again. The third focus of this study lies on testing the transferability of the animal models to human samples. In this proof-of-concept approach, Raman spectra of human samples (adenoma, carcinoma, normal mucosa) are recorded in order to evaluate the comparability with the measurements on mouse tissue sections. In case such a comparability is given the results/models from the mouse study can be directly adopted. If the comparability is not guaranteed first tests should be performed to unravel a Raman cancer signature in humans. All these studies have the goal to better understand the Raman based cancer diagnostics, its potential and its limitations.