ABSTRACT
Cyclin B2 (CCNB2), a member of the cyclin protein family, has been found to be up-regulated in human cancers. To evaluate the potential use of circulating CCNB2 in serum in cancer surveillance, we examined relative expression levels of serum circulating CCNB2 mRNA in 103 cancer patients, 19 normal controls, and 40 benign disease patients using real-time quantitative reverse transcriptase polymerase chain reaction. We found that the relative expression level of circulating CCNB2 mRNA in cancer patients was significantly higher (p<0.0001) than that in normal controls and benign diseases group. Circulating CCNB2 mRNA level was significantly (p<0.001) correlated with cancer stage and metastasis status. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.87 and 0.83 (p<0.05) in identifying cancer patients' metastasis status in lung and digestive tract cancer, respectively. Moreover, we observed that expression levels of circulating CCNB2 mRNA in cancer patients significantly decreased (p=0.0084) after their therapeutic treatments. These data suggest that detection of serum circulating CCNB2 mRNA may have potential clinical applications in screening and monitoring of metastasis and therapeutic treatments.
Subject(s)
Biomarkers, Tumor/blood , Cyclin B2/blood , Neoplasms/diagnosis , RNA, Messenger/blood , Aged , Case-Control Studies , Cyclin B2/genetics , Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/pathology , Female , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/pathology , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasms/pathology , Transcriptional Activation , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathologyABSTRACT
Cyclin B2 (CCNB2), a member of the cyclin protein family, has been found to be up-regulated in human cancers. To evaluate the potential use of circulating CCNB2 in serum in cancer surveillance, we examined relative expression levels of serum circulating CCNB2 mRNA in 103 cancer patients, 19 normal controls, and 40 benign disease patients using real-time quantitative reverse transcriptase polymerase chain reaction. We found that the relative expression level of circulating CCNB2 mRNA in cancer patients was significantly higher (p<0.0001) than that in normal controls and benign diseases group. Circulating CCNB2 mRNA level was significantly (p<0.001) correlated with cancer stage and metastasis status. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.87 and 0.83 (p<0.05) in identifying cancer patients' metastasis status in lung and digestive tract cancer, respectively. Moreover, we observed that expression levels of circulating CCNB2 mRNA in cancer patients significantly decreased (p=0.0084) after their therapeutic treatments. These data suggest that detection of serum circulating CCNB2 mRNA may have potential clinical applications in screening and monitoring of metastasis and therapeutic treatments.
ABSTRACT
The HSulf-1 gene is an important factor that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix, resulting in disturbance of HSPG-related signal transduction pathways. Recently, HSulf-1 has been reported to be down-regulated in several human cancers. In this study, we first cloned and characterized the 5' promoter region of the HSulf-1 gene (around 400 bp) that contained high basal promoter activity. We also found that this functional promoter region was hypermethylated in a number of human cancer cell lines. Furthermore, we found that hypermethylation in this promoter region correlated with the down-regulation of the HSulf-1 expression in human breast and gastric cancer cell lines and tissue samples. These results suggest that the promoter hypermethylation may be one of the mechanisms of the HSulf-1 gene silencing in human breast and gastric cancers. Finally, we demonstrated that the HSulf-1 promoter was more frequently (p<0.05) methylated in cell-free DNA extracted from serum samples of human breast and gastric cancer patients than that of healthy people (76.2%, 55.0% and 19.0%, respectively), indicating that detection of the HSulf-1 promoter methylation in serum samples may have clinical implications in early detection and diagnosis of human breast and gastric cancers.
