SUMMARY

Our group has described an EGFR-centric secretome induced by cetuximab in 3D spheroids of colorectal cancer cells. Furthermore, in plasma of colorectal cancer patients we have identified and preliminarily validated that phosphorylated-EGFR is a candidatesecreted biomarker of response to cetuximab. We have also shown that intracellular and extracellular signaling are connected in tumor cells, and how this connection can lead to the non-invasive monitoring of anti-EGFR treatment in patients with colorectal cancer.

We have also developed and implemented a normalization algorithm that corrects the statistical results of secretome-based comparative proteomic studies by the global protein secretion rate of cells. The application of this normalization to two different biological scenarios altered the statistical significance of several secreted proteins. In an epithelial-to-mesenchymal transition (EMT), known EMT effectors were only statistically significant when the normalization was applied. Therefore, the cell-centric normalization of secretomes increases the sensitivity of statistical tests by increasing the number of true-positives among the list of candidate biomarkers.

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