Evaluation of desmoplastic and replacement type histopathological growth patterns of colorectal cancer liver metastases at single-cell resolution

by Johannes Robert Fleischer
Cumulative thesis
Date of Examination:2024-09-20
Date of issue:2024-09-10
Advisor:PD Dr. Dr. Lena-Christin Conradi
Referee:Prof. Dr. Argyris Papantonis
Referee:Prof. Dr. Matthias Dobbelstein
Persistent Address: http://dx.doi.org/10.53846/goediss-10729

 

 

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Abstract

English

This thesis project evaluated molecular differences between desmoplastic and replacement colorectal liver metastases, with the focus on the heterogeneity between ECs in livers colonized by CRCLM. Stratifying the sample specimen according to their mode of blood irrigation into sprouting angiogenesis or vessel cooption, I used a single cell RNA sequencing pipeline to establish a comprehensive dataset that captured all main cell populations. After conducting extensive literature research and publishing my findings, I focused on studying the heterogeneity of endothelial cells in the adjacent liver. This exploration revealed a connection between the HGP/mode of vascularization and the presence of a unique capillary phenotype that had not been previously described. This discovery implicates a possible contribution of the host microenvironment to the development of different phenotypes. Moreover, I discussed if this discovery might be correlating to a previously not proven association of liver fibrosis and the observation of desmoplastic CRCLM. Further research might use these findings to evaluate possible mechanistical connections between cancer cells and the endothelial cells or the possibility to tailor targeted personalized treatment regimes.
Keywords: Cancer; Colorectal Liver Metastases; Liver Metastases; Vessel; Vessel Co-option; Oncology; Sprouting Angiogenesis