Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis
Menée sur des échantillons sanguins prélevés sur une cohorte initiale de 381 patients atteints d'un cancer colorectal, puis validée sur une cohorte complémentaire de 330 patients, cette étude suggère que le niveau d'expression de PLS3 pourrait servir de biomarqueur pour la détection de cellules tumorales circulantes
Circulating tumor cells (CTCs) in the blood have attracted attention as biomarkers and seeds of metastasis. However, systems that detect CTC on the basis of epithelial markers (e.g., EpCAM, cytokeratins) may miss many tumor cells as a result of marker downregulation after epithelial-mesenchymal transition (EMT). The purpose of this study was to define CTC-based prognostic markers in colorectal cancer that are not repressed by EMT. Here we report Plastin3 (PLS3) as a novel CTC marker associated with with invasive and metastatic capabilities of colorectal cancer cells. Employing a qRT-PCR assay specific for PLS3, peripheral blood samples of CRC patients were analyzed (training set, n = 381; validation set, n = 330). PLS3 was not expressed by normal blood cells. Its expression was high in metastatic CRC cells and it was not downregulated during EMT. Detection of PLS3-positive CTC in peripheral blood was associated with reduced overall patient survival. Multivariate analysis showed that this prognostic influence was independent from established risk factors. In particular, in Dukes grade B and C patients, detection of PLS3-positive CTC was determined to be the most significant prognostic factor, surpassing other currently available clinicopathological factors. Our results firmly establish PLS3 as a novel marker for the detection of metastatic CRC cells in the blood, offering a significant value compared to other known prognostic factors.
Cancer Research , résumé, 2013