Methylation pattern of oncogene HRAS gene promoter region and its clinical relevance to urocystic tumorigenesis.

The HRAS gene encodes a protein with a molecular weight of 21 kDa (P21) called H-Ras that is involved primarily in regulating cell growth, division and apoptosis. Through a process known as signal transduction, the H-Ras protein relays signals from outside of the cell to the cell's nucleus. These signals instruct the cell to grow or divide. HRAS is in the Ras family of oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous cells. Considering the upsurge of evidences that abnormality in CpG methylation of the oncogene promoter region can cause cancer, we want to understand the relationships between the methylation status of the HRAS promoter region and bladder cancer. To investigate the methylation pattern of HRAS gene transcriptional regulation region (TRR), bisulfite-sequencing PCR-based sequencing analysis was performed among 15 bladder cancer tissues and 5 normal bladder tissues. Analysis of HRAS gene TRR methylation showed that the methylation level of HRAS has clinical relevance (P = 0.0049, by unpaired Student's t test) with bladder cancer. Furthermore, the unpaired Student's t test analysis showed the extremely significant relationship between tumor and normal at CpG site of the 3rd (P < 0.0001), 28th (P = 0.0006), and significant association between tumor and methylation at CpG site of the 12th (P = 0.0024). Abnormal methylation of the HRAS gene may be an early event during urocystic tumorigenesis and may be further used as a cancer biomarker in bladder tissue for early diagnosis and a potential therapeutic target.