Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer.

Abstract

Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options. Even after successful surgical resection of the primary tumor, metachronous liver metastases occur in one out of eight cases. The only available curative intended treatment is hepatic resection, but metachronous CRLM frequently recur after approximately 1 year. In this study, we performed a proteome analysis of three recurrent liver metastases of a single CRC patient by mass spectrometry. Despite surgical resection of the primary CRC and adjuvant chemotherapy plus cetuximab treatment, the patient developed three metachronous CRLM which occurred consecutively after 9, 21 and 31 months. We identified a set of 1132 proteins expressed in the three metachronous CRLM, of which 481 were differentially regulated, including 81 proteins that were associated with the extracellular matrix (ECM). 56 ECM associated proteins were identified as upregulated in the third metastasis, 26 (46%) of which were previously described as negative prognostic markers in CRC, including tenascin C, nidogen 1, fibulin 1 and vitronectin. These data may reflect an ascending trend of malignancy from the first to the third metachronous colorectal cancer liver metastasis. Additionally, the results indicate different ECM phenotypes for recurrent metachronous metastasis, associated with different grades of malignancy and highlights the importance of individual analysis of molecular features in different, consecutive metastatic events in a single patient.

• Authors: Hannah Voß, Marcus Wurlitzer, Daniel J Smit, Florian Ewald, Malik Alawi, Michael Spohn, Daniela Indenbirken, Maryam Omidi, Kerstin David, Hartmut Juhl, Ronald Simon, Guido Sauter, Lutz Fischer, Jakob R Izbicki, Mark P Molloy, Björn Nashan, Hartmut Schlüter, Manfred Jücker
• Journal: Clinical & experimental metastasis (Clin Exp Metastasis) Vol. 37 Issue 6 Pg. 649-656 (12 2020) ISSN: 1573-7276 [Electronic] Netherlands
• PMID: 33099724 (Publication Type: Journal Article)

Chemical References

• Extracellular Matrix Proteins
• Organoplatinum Compounds
• Proteome
• Leucovorin
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Extracellular Matrix (metabolism, pathology)
• Extracellular Matrix Proteins (metabolism)
• Fluorouracil (administration & dosage)
• Humans
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, metabolism, secondary)
• Male
• Mass Spectrometry
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, metabolism, pathology)
• Neoplasms, Second Primary (drug therapy, metabolism, pathology)
• Organoplatinum Compounds (administration & dosage)
• Proteome (metabolism)