Abstract
IntroductionColorectal cancer (CRC) represents a relevant public health problem. Despite new therapeutic advances, prognosis of patients diagnosed with advanced disease is still poor. The identification of new markers involved in the mechanisms of invasiveness represents a priority in order to better understand cancer development and generate new therapeutic targets. We describe here the possible role of EPDR1, a gene not yet well characterised, which encodes a protein related to ependymins, a family of piscine transmembrane proteins involved in cell adhesion.To evaluate the role of EPDR1, a translational investigation was planned to explore the consequences of the upregulation of EPDR1 in cell models and in a well- balanced cohort of patients diagnosed with localised CRC.Material and methodsExpression of EPDR1 was determined by RT-qPCR in several CRC cell lines and in paired samples derived from CRC patients. The effects of silencing the gene on cell proliferation, invasion, migration and adhesion was studied in vitro.147 patients diagnosed with localised disease, belonging to different stages, were prospectively selected in a single institution, according to different clinicopathological features such as stage, grading and MSI. All medical histories and the pathologic reports were reviewed. All patients signed an informed consent at time of diagnosis. RNA was extracted form paraffin embedding samples of each primary tumour.The statistical system R was used for all analyses.Results and discussionsKnockdown of the gene results in a decrease of cell proliferation, adhesion to collagen-coated plates, invasion and migration, while it was possible to observe an increase in necrosis among CRC cell lines.140 patients were finally selected to perform the analysis, 7 were excluded because of the presence of secondary malignancy.EPDR1 is more expressed in tumour than normal tissue among patients diagnosed with CRC. Interestingly, EPDR1 expression is directly related to T parameter, being higher among patients diagnosed with T3 and T4 CRC, independently from nodal involvement.ConclusionEPDR1 seems to be a new marker of tumour invasiveness in CRC patients and its detection could predict tumour infiltration.
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