Kinase substrate protein microarray analysis of human colon cancer and hepatic metastasis

Claudio Belluco*, Enzo Mammano, Emanuel Petricoin, Luca Prevedello, Valerie Calvert, Lance Liotta, Donato Nitti, Mario Lise

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Background: Liver metastases represent the major determinant of survival in patients with colorectal cancer (CRC). In cases with unresectable liver disease, more effective agents are needed, since chemotherapy achieves median survival of only 15 months. Protein kinases coordinate complex functions that are often disregulated in cancer and are therefore considered important targets for molecular therapeutics. In this study, we investigated the phosphoproteomic status of different protein kinases in primary CRC and in liver metastases. Methods: The status of 29 key endpoints was evaluated using reverse phase protein array on laser capture microdissected neoplastic cells from five primary CRCs without metastases, three patient-matched primary CRCs and synchronous liver metastases and five CRC metachronous liver metastases. Results: Unsupervised hierarchical two-way clustering analysis showed an entirely different phosphoproteomic profile in primary CRCs compared to liver metastases. This difference was observed also in primary and metastatic patient-matched lesions. Conclusions: Our findings of different signaling pathways between primary and metastatic CRC suggest a possible microenvironment effect, and emphasize the need to perform molecular network analysis of metastatic tissue when molecular targeting is considered.

Original languageEnglish
Pages (from-to)180-183
Number of pages4
JournalClinica Chimica Acta
Issue number2
StatePublished - 24 Jul 2005
Externally publishedYes


  • Colorectal cancer
  • Metastasis
  • Protein kinases
  • Proteomics


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