Kriukova Elena, Mazurenka Mikhail, Marcazzan Sabrina, Tschurtschenthaler Markus, Puppels Gerwin, Glasl Sarah, Saur Dieter, Jesinghaus Moritz, Pouliou Marialena, Agelopoulos Marios, Klinakis Apostolos, Quante Michael, Ripoll Jorge, Ntziachristos Vasilis, Gorpas Dimitris
Chair of Biological Imaging, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health & School of Computation, Information and Technology, Technical University of Munich, Munich 81675, Germany.
Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, Neuherberg 85764, Germany.
Anal Chem. 2025 Jun 24;97(24):12642-12653. doi: 10.1021/acs.analchem.5c00954. Epub 2025 Jun 11.
Field cancerization (FC) refers to spatially distributed premalignant tissue changes that lead to the appearance of local malignancy, and its detection can improve cancer screening. In this work, we employ combined Raman and partial wave spectroscopy (RS-PWS) to detect FC in gastroesophageal (L2-IL1B) and intestinal (Villin-Cre, Apc) tumor mouse models. Using a hybrid RS-PWS microscope, we acquire both molecular and morphological information from macroscopically normal tumor-adjacent tissue and investigate the individual and combined performance of each modality. For data analysis, we use partial least-squares discriminant analysis (PLS-DA). In the normal tissue of L2-IL1B mice, we demonstrate a statistically significant increase ( < 0.001) in Raman band intensities associated with free amino acids and a decrease in bands associated with lipids ( < 0.005) and carotenoids ( < 0.001) compared to healthy controls. Similarly, in the normal mucosa of Villin-Cre, Apc mice, the intensities of RS bands associated with amino acids increase significantly ( < 0.05) compared to controls, while the intensities of lipid-associated bands decrease significantly ( < 0.05). Transcriptomic profiling using RNA-sequencing analysis on these samples identified a significant correlation between gene expression and optical findings. Moreover, we demonstrate that combining RS and PWS data further improves the significance of our classification results. When macroscopically normal tumor-adjacent tissue is compared with tissue from healthy controls, we observe that PWS increases the of RS results by ∼9% in L2-IL1B mice and ∼5% in Villin-Cre, Apc mice. Combining molecular RS with structural PWS information enhances the ability to detect precancerous changes and provides insights into tissue alterations during cancer development.
场癌化（FC）是指导致局部恶性肿瘤出现的空间分布的癌前组织变化，其检测可改善癌症筛查。在本研究中，我们采用拉曼光谱和分波光谱联用技术（RS-PWS）检测胃食管（L2-IL1B）和肠道（Villin-Cre，Apc）肿瘤小鼠模型中的场癌化。使用混合式RS-PWS显微镜，我们从宏观正常的肿瘤邻近组织获取分子和形态学信息，并研究每种模式的单独和联合性能。对于数据分析，我们使用偏最小二乘判别分析（PLS-DA）。在L2-IL1B小鼠的正常组织中，与健康对照相比，我们发现与游离氨基酸相关的拉曼谱带强度有统计学显著增加（<0.001），与脂质（<0.005）和类胡萝卜素（<0.001）相关的谱带强度降低。同样，在Villin-Cre，Apc小鼠的正常黏膜中，与氨基酸相关的RS谱带强度与对照相比显著增加（<0.05），而与脂质相关的谱带强度显著降低（<0.05）。对这些样本进行RNA测序分析的转录组谱分析确定了基因表达与光学结果之间的显著相关性。此外，我们证明将RS和PWS数据相结合可进一步提高我们分类结果的显著性。当将宏观正常的肿瘤邻近组织与健康对照组织进行比较时，我们观察到在L2-IL1B小鼠中PWS使RS结果的 提高了约9%，在Villin-Cre，Apc小鼠中提高了约5%。将分子RS与结构PWS信息相结合可增强检测癌前变化的能力，并为癌症发展过程中的组织改变提供见解。
