Prognostic impact of GPR56 in patients with colorectal cancer.

G protein-coupled receptor 56 (GPR56) belongs to the adhesion G protein-coupled receptor subfamily, which plays a role in cell progression and survival. The aim of this study was to investigate the role of the GPR56 gene in a cell line study and the impact of its protein expression on the prognosis of colorectal cancer (CRC) patients. The effect of GPR56 on tumor cell proliferation (WST-1 assay), invasion (Transwell assay), migration (Transwell assay, wound healing assay), and colony-forming ability (semisolid agar colony-forming assay) was explored. The expression levels of GPR56 in tissue samples of 109 CRC patients were evaluated by immunohistochemistry. The prognostic value of GRP56 was analyzed using univariate and multivariate analyses. The downregulation of GPR56 in the CRC cell line reduced cell proliferation as compared with that in a control sample (48 h; p=0.042, 72 h; p=0.001). Downregulation of the GPR56 expression reduced cell invasion and migration abilities and inhibited colony-forming abilities (p<0.005). The 5-year overall survival rate was worse in the high-expression group as compared with that in the low-expression group (51.6% vs. 74.4%, p=0.008). High GPR56 expression was a significant prognostic factor for overall survival of CRC patients in the univariate (p=0.001) and multivariate (p<0.001) analyses. The expression level of GPR56 plays an important role in tumor progression in CRC, and it may serve as a prognostic indicator in CRC patients.

Expression of AMP-activated protein kinase/ten-eleven translocation 2 and their clinical relevance in colorectal cancer.

Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.