Relationship of promoter methylation and mRNA expression of RAS-related domain family 5Agene in peripheral blood of lyphoma patients with clinical manifestations of the patients
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Abstract:
Objective:To investigate the promoter methylation status of Ras-association domain family 5A (RASSF5A) gene and its mRNA expression level in in the peripheral blood of patients with lymphoma and normal people as well as its correlation to clinical manifestations. Methods:Methylation-specific PCR (MSP) and Reverse Transcriptase-PCR(RT-PCR) method were used to examine the methylation status and the mRNA expression of RASSF5A gene in peripheral blood of patients with diffused large B cell lymphoma or T cell lymphoma and healthy participants. The relationship between RASSF5Agene methylation and clinical data was further analyzed. Results: The methylation frequencies of RASSF5A in diffused large B cell lymphoma and T cell lymphoma (64.9% \[48/74\] and 73.8% \[31/42\]) were significantly higher than that of healthy participants (7.1% \[3/42\], all P<0.05). The mRNA expressions of RASSF5A gene in diffused large B cell lymphoma and peripheral T cell lymphoma were (0.54±0.17) and (0.52±0.18), respectively, which were significantly lower than that of healthy participants (0.86±0.10) (P<0.05). The mRNA expression of RASSF5A gene with positive promoter methylation (\[0.51±0.18\]; \[0.50±0.15\]) was significantly lower than that of the gene with negative methylation (\[0.60±0.17\]; \[0.63±0.12\]) (all P<0.05) in both diffused large B cell lymphoma and T cell lymphoma. Methylation frequency of RASSF5A gene was associated with LDH, IPI, and Ki-67 (P<0.05) in diffused large B cell lymphoma, and associated with clinical stage, extranodal involvement and Ki-67 (P<0.05) in T cell lymphoma. The mRNA expression of RASSF5A gene was correlated with IPI score, extranodal involvement (P<0.05) in diffused large B cell lymphoma, and correlated with clinical stage and extranodal involvement (P<0.05) in T cell lymphoma. Conclusion: The methylation of RASSF5A gene may be associated with the occurrence of diffused large B cell lymphoma and T cell lymphoma, and mRNA expression silencing might be one of the mechanisms of epigenetics. RASSF5A gene may act as a tumor suppressor gene in diffused large B cell lymphoma and T cell lymphoma, which may be associated with tumor invasiveness, tumor malignant process and tumor prognosis.
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Project supported by the National Natural Science Foundation of China (No. 81472335)