Identification of secretory gelsolin as a plasma biomarker associated with distant organ metastasis of colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide. More than half of all CRC patients will develop metastases, which represents the major cause of death for CRC patients. CRC metastases confined in other organs are potentially resectable, and patients who receive curative resections appear to have better outcomes. Thus, the early detection of metastasis in CRC patients could improve their survival rate after curative surgery. Here, we report the use of Cy-dye labeling combined with multi-dimensional fractionation and mass spectrometry as a proteomics-based approach for identifying CRC metastasis-associated biomarker(s) in plasma samples collected from three CRC patients upon diagnosis of their primary and metastatic tumors. Among the eight identified proteins, we used Western blot analysis and an in-house-developed ELISA to validate the increased plasma levels of one, secretory (plasma) gelsolin, in >80% of CRC patients with distal metastases in a larger sample cohort (32 patients). We also found a significant increase of secretory gelsolin in plasma samples of stage IV versus stages I-III CRC patients before treatment. Furthermore, immunohistochemistry showed that secretory gelsolin was highly overexpressed in CRC tissue specimens compared to adjacent normal tissues, and a cell model study showed that secretory gelsolin may help regulate CRC cell migration.