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Characterization of spatial heterogeneity in metastasized colorectal cancer by MALDI imaging

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 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.

INSTRUMENT(S): 4800 Plus MALDI TOF/TOF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Lennart Moritz

LAB HEAD: Melanie Föll

PROVIDER: PXD039409 | Pride | 2023-02-17

REPOSITORIES: Pride

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Project description:Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has recently gained prominence for its ability to provide molecular and spatial information in tissue sections. This technology has the potential to uncover novel insights into proteins and other molecules in biological and immunological pathways activated along diseases with a complex host-pathogen interaction, such as animal tuberculosis. Thus, the present study conducted a data analysis of protein signature in granulomas of cattle and pigs naturally infected with Mycobacterium tuberculosis complex (MTC), identifying biological and immunological signalling pathways activated throughout the disease. Lymph nodes from four pigs and cattle, positive for MTC by bacteriological culture and/or real-time PCR, were processed for histopathological examination and MALDI-MSI. Protein identities were assigned using the MaTisse database, and protein-protein interaction networks were visualized using the STRING database. Gene ontology (GO) analysis was carried out to determine biological and immunological signalling pathways in which these proteins could participate together with KEGG analysis. Distinct proteomic profiles between cattle and pig granulomas were displayed. Noteworthy, the GO analysis revealed also common pathways among both species, such as â€œComplement activation, alternative pathwayâ€� and â€œTricarboxylic acid cycleâ€�, which highlights pathways that are conserved among different species infected by MTC. In addition, species-specific terms were identified in the current study, such as â€œNatural killer cell degranulationâ€� in cattle or those related to platelet and neutrophils recruitment and activation in pigs. Overall, this study provides insights into the immunopathogenesis of tuberculosis in cattle and pigs, opening new areas of research and highlighting the importance, among others, of the complement activation pathway and the regulation of natural killer cell and neutrophil-mediated immunity in this disease.

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Characterization of spatial heterogeneity in metastasized colorectal cancer by MALDI imaging

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