Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Characterization of Spatial Heterogeneity in Metastasized Colorectal Cancer by MALDI Imaging

Lennart Moritz
,
Maren Nicole Stillger
,
Ferenc Takács
ORCID logo ,
Hannah Füllgraf
,
Martin Werner
,
Stefan Fichtner-Feigl
,
Andreas Jud
,
Oliver Schilling
ORCID logo ,
Melanie Christine Föll
*
Version 1 : Received: 17 February 2023 / Approved: 21 February 2023 / Online: 21 February 2023 (11:21:41 CET)

How to cite: Moritz, L.; Stillger, M.N.; Takács, F.; Füllgraf, H.; Werner, M.; Fichtner-Feigl, S.; Jud, A.; Schilling, O.; Föll, M.C. Characterization of Spatial Heterogeneity in Metastasized Colorectal Cancer by MALDI Imaging. Preprints 2023, 2023020363. https://doi.org/10.20944/preprints202302.0363.v1 Moritz, L.; Stillger, M.N.; Takács, F.; Füllgraf, H.; Werner, M.; Fichtner-Feigl, S.; Jud, A.; Schilling, O.; Föll, M.C. Characterization of Spatial Heterogeneity in Metastasized Colorectal Cancer by MALDI Imaging. Preprints 2023, 2023020363. https://doi.org/10.20944/preprints202302.0363.v1

Abstract

About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor treatment response and clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient-matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient-matched liver metastases.

Keywords

colorectal cancer; metastasis; tumor heterogeneity; spatial proteomics; mass spectrometry imaging; MALDI imaging; formalin-fixed paraffin-embedded tissues

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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