Role of serine/threonine kinase 33 methylation in colorectal cancer and its clinical significance

摘要

Serine/threonine kinase 33 (STK33) is a novel protein that has been the focus of an increasing number of studies in recent years; however, the role of STK33 in tumorigenesis remains controversial. Previous studies have demonstrated that STK33 is overexpressed in several human cancers and exerts a pro-tumorigenic effect through the promotion of cell proliferation. However, the role of STK33 in colorectal cancer (CRC), which is one of the most aggressive human malignancies, remains unclear. The aim of the current study was to investigate the methylation status of STK33 in CRC and to determine its clinical significance. The results demonstrated that STK33 was hypermethylated in CRC cell lines and promoted the proliferation of CRC cells. In addition, the methylation status and expression of STK33 in 94 pairs of cancer and noncancerous tissues obtained from patients with CRC was investigated. STK33 methylation was significantly increased in cancer tissues when compared with adjacent noncancerous tissues (P0.001). STK33 methylation was associated with lymph node metastasis (P0.05), tumor invasion (P0.05), distant metastases (P0.01) and tumor stage (P0.01). Reduced STK33 mRNA and protein expression in CRC was associated with STK33 hypermethylation (P0.001). In addition, patients with hypermethylated STK33 exhibited shorter overall survival rates when compared with those with unmethylated STK33 (P0.01). In conclusion, the results of the current study suggest that STK33 hypermethylation may be a promising novel biomarker for the diagnosis, prognosis and suitable treatment of CRC.