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

在本建议的背景下，应当通过对腺瘤-癌-序列的光谱建模、不同人群对基于拉曼的诊断模型的影响以及诊断模型在人体样本上的可转移性来进一步评估基于拉曼光谱的有效和快速的组织诊断的基础。基于已获得的拉曼数据，研究了腺瘤-癌-序列的光谱模拟，以得出在致癌过程中的光谱变化。基于此建模，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信号做出可靠的诊断。此外，还计划对不同遗传倾向的动物进行单独研究。需要回答的问题是，这些人群的致癌机制是否不同，因此，基于拉曼的诊断方法必须反映这些差异。这可以通过构建两个群体的拉曼诊断模型并随后比较这些模型的光谱分布和分类准确性来进行测试。在这样做的过程中，两个种群都需要大量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资助期开始使用，因此只有几个数据需要重新测量。这项研究的第三个重点是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，记录了人类样本(腺瘤、癌、正常粘膜)的拉曼光谱，以评估其与小鼠组织切片测量的可比性。在给出这种可比性的情况下，可以直接采用来自小鼠研究的结果/模型。如果不能保证可比性，首先应该进行测试，以揭示人类的拉曼癌症特征。所有这些研究的目的都是为了更好地理解基于拉曼的癌症诊断，它的潜力和局限性。

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.