Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with co
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RESEARCH PAPER
Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer Hannah Voß1 · Marcus Wurlitzer1 · Daniel J. Smit2 · Florian Ewald3 · Malik Alawi4 · Michael Spohn5 · Daniela Indenbirken5 · Maryam Omidi1 · Kerstin David6 · Hartmut Juhl6 · Ronald Simon7 · Guido Sauter7 · Lutz Fischer8 · Jakob R. Izbicki3 · Mark P. Molloy9 · Björn Nashan8,10 · Hartmut Schlüter1 · Manfred Jücker2 Received: 14 July 2020 / Accepted: 8 October 2020 © The Author(s) 2020
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. Keywords Colorectal cancer · Colorectal liver metastasis · CRC · CRLM · Metachronous liver metastasis · Proteomics · Extracellular matrix · ECM · ECM signatures · Prognostic factor Abbreviations 5-FU 5-Fluorouracil CRC Colorectal cancer CRLM Colorectal cancer liver metastases DCN Decorin ECM Extracellular matrix Hannah Voß, Marcus Wurlitzer, Daniel J. Smit and Florian Ewald have contributed equally as first authors to this work. Hartmut Schlüter and Manfred Jücker have contributed equally as last authors to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10585-020-10058-8) contains supplementary material, which is available to authorized users.
F13A1 Coagulation factor XIII A chain H&E Haematoxylin and eosin
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