Abstract
Simple SummaryColorectal cancer (CRC) is the third leading cause of cancer death in both sexes. Identification of the influencing factors and molecular mechanisms in CRC progression could improve patient survival. This study aimed first to characterize the expression of Discoidin Domain Receptor 1 (DDR1), a receptor tyrosine kinase for collagens in a large cohort of CRC patients, and second to establish in vitro whether DDR1 expression level is linked to CRC aggressiveness potential. Our immunohistochemical study indicated that DDR1 is highly expressed in colon cancer compared to normal colonic mucosa and its expression is associated with shorter event-free survival. In vitro, the invasive properties of several CRC cell lines seem to be correlated with the expression level of DDR1. Taken altogether, our results show that DDR1 is highly expressed in most colon adenocarcinomas and appears as an indicator of worse event free survival.Extracellular matrix components such as collagens are deposited within the tumor microenvironment at primary and metastatic sites and are recognized to be critical during tumor progression and metastasis development. This study aimed to evaluate the clinical and prognostic impact of Discoidin Domain Receptor 1 (DDR1) expression in colon cancers and its association with a particular molecular and/or morphological profile and to evaluate its potential role as a prognosis biomarker. Immunohistochemical expression of DDR1 was evaluated on 292 colonic adenocarcinomas. DDR1 was highly expressed in 240 (82.2%) adenocarcinomas. High DDR1 immunostaining score was significantly associated, on univariate analysis, with male sex, left tumor location, BRAF wild type status, KRAS mutated status, and Annexin A10 negativity. High DDR1 immunohistochemical expression was associated with shorter event free survival only. Laser capture microdissection analyses revealed that DDR1 mRNA expression was mainly attributable to adenocarcinoma compared to stromal cells. The impact of DDR1 expression on cell invasion was then evaluated by modified Boyden chamber assay using cell types with distinct mutational profiles. The invasion capacity of colon adenocarcinoma is supported by DDR1 expression. Thus, our results showed that DDR1 was highly expressed in most colon adenocarcinomas and appears as an indicator of worse event free survival.
Highlights
Colorectal cancer (CRC) is ranked among the most common cancers in the world and is a significant public health issue in developed countries
We investigated the expression of Discoidin Domain Receptor 1 (DDR1) using immunohistochemistry in colon adenocarcinoma and studied the link between DDR1 expression with clinicopathologic and molecular parameters, including overall and event-free survival
Because DDR1 seems to play a role in CRC cell invasion and metastasis [5], we investigated the impact of DDR1 on invasion properties of CRC cell lines in vitro using type I collagen as a main extracellular matrix component
Summary
Colorectal cancer (CRC) is ranked among the most common cancers in the world and is a significant public health issue in developed countries. Recent data indicated that CRC is the third most common cancer and the second leading cause of cancer death in both sexes [1]. About 39% of CRC patients are diagnosed at early stage with localized-stage disease. At the same stage, all CRC do not have the same prognosis. New biomarkers able to stratify the prognosis groups of patients and improve treatment strategies remain necessary. For this purpose, several studies investigate the signaling pathways that promote the metastatic process in CRC in order to identify new key players in this process that could constitute potential targets [4]
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