Abstract
ABSTRACT Background Protein tyrosine kinase-7 (PTK7) is a receptor tyrosine kinase (TK), with no identified natural ligand and a catalytically inactive intracellular TK domain. PTK7 expression is up-regulated in many human cancers, including colorectal cancer (CRC), but little is known about its role in cancer biology. Here, we have examined PTK7 protein expression in tumor and matched normal tissues from CRC patients by immunohistochemistry (IHC) and addressed the phenotypic impact of PTK7 down-regulation in CRC cell lines. Methods A TMA containing both tumor and matched normal tissues was built from a cohort of 192 patients with CRC collected between 1990 and 1998 at the Institut Paoli-Calmettes, Marseille, France. PTK7 expression was analyzed by IHC using polyclonal goat antibody anti-CC4 (RD sex ratio = male (52%), female (48%); site = colon (90%), rectum (10%); stage = I-III (64%), IV (36%); median follow-up = 104 months. Staining intensity (0-1 = 65% of cases, 2 = 19% of cases, 3 =16% of cases, in tumor tissues versus 0-1 = 86% of cases, 2 = 11% of cases, 3= 3% of cases, in normal tissues; p = 1,91.10-8) as well as average percentage of stained cells (30% in tumor tissues versus 2% in normal tissues; p = 5.74.10-14) were higher in tumor compared to normal tissues. In stage I-III population (n = 122), 5-year MFS was lower in PTK7-positive (>10% of cells stained with intensity > 2) compared to PTK7-negative CRC (54% [95%CI: 38-75%] versus 75% [95%CI: 65-88%], p = 0.034, log-rank test). This impact was maintained in multivariate analysis and similar trends were observed in overall survival, while not reaching statistical significance. In vitro, PTK7 inhibition by shRNA significantly reduced cell migration. Conclusion PTK7 protein is overexpressed in CRC and is associated with reduced MFS, possibly due to an impact on cell migration. Disclosure All authors have declared no conflicts of interest.
Published Version
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