Objective: To explore the methylation status of shp1 gene in plasma DNA from patients with diffuse large B cell lymphoma (DLBCL) and discuss its possible application in molecular diagnosis and targeted therapy of the disease.
Methods: Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation status of shp1 gene in plasma and peripheral blood leukocytes (PBLs) of 35 DLBCL patients. The formaldehyde-fixed, paraffin-embedded (FFPE) tumor tissue samples were collected from 28 DLBCL patients, 6 patients of benign lymphoid hyperplasia and 13 healthy volunteers were selected as nonmalignant controls from January 2012 to December 2013. Methylation frequencies of shp1 gene in different groups were compared and the associations of shp1 methylation status with clinicopathological characteristics were analyzed.
Results: No methylation of shp1 was detected in any of the 19 nonmalignant controls. The methylation rate of shp1 in plasma, PBLs and FFPE tumor tissues from patients with DLBCL was 51.4% (18/35), 28.6% (10/35) and 64.3% (18/28) respectively; there was a high methylation consistency of shp1 between plasma and FFPE tumor tissues (κ = 0.78, P = 0.00).However, methylation consistency was lower between PBLs and FFPE tumor tissues (κ = 0.36, P = 0.01). Methylation of shp1 was frequently detected in plasma and FFPE tumor tissues samples from patients with a high serum level of lactate dehydrogenase (13/16 vs 5/19, 11/12 vs 7/16, P = 0.02, 0.04) .However, no such association was detected in PBLs (P = 0.14).
Conclusions: Methylation of shp1 in plasma DNA can represent shp1 methylation status in tumor tissue. And it may serve as a promising biomarker in aiding DLBCL diagnosis and guiding targeted therapy.